{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T13:13:29Z","timestamp":1770297209363,"version":"3.49.0"},"reference-count":258,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MIUR PRIN","award":["2017RKWNJT"],"award-info":[{"award-number":["2017RKWNJT"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as the subsequent organ formation via the temporal and spatial regulation of cell proliferation and differentiation. However, aberrant activation of HH signaling has been identified in a broad range of malignant disorders, where it positively influences proliferation, survival, and therapeutic resistance of neoplastic cells. Inhibitors targeting the HH pathway have been tested in preclinical cancer models. The HH pathway is also overactive in other blood malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). This review is intended to summarize our knowledge of the biological roles and pathophysiology of the HH pathway during normal T-cell lymphopoiesis and in T-ALL. In addition, we will discuss potential therapeutic strategies that might expand the clinical usefulness of drugs targeting the HH pathway in T-ALL.<\/jats:p>","DOI":"10.3390\/ijms24032962","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T02:35:10Z","timestamp":1675391710000},"page":"2962","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL)"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-7260","authenticated-orcid":false,"given":"Alberto M.","family":"Martelli","sequence":"first","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Paganelli","sequence":"additional","affiliation":[{"name":"CNR-Institute of Molecular Genetics \u201cLuigi Luca Cavalli-Sforza\u201d, Unit of Bologna, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Truocchio","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0587-0112","authenticated-orcid":false,"given":"Carla","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neuronal Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Chiarini","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neuronal Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-3156","authenticated-orcid":false,"given":"James A.","family":"McCubrey","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/287795a0","article-title":"Mutations affecting segment number and polarity in Drosophila","volume":"287","author":"Wieschaus","year":"1980","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1101\/gad.938601","article-title":"Hedgehog signaling in animal development: Paradigms and principles","volume":"15","author":"Ingham","year":"2001","journal-title":"Genes. Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1101\/gad.1693608","article-title":"Hedgehog: Functions and mechanisms","volume":"22","author":"Varjosalo","year":"2008","journal-title":"Genes. Dev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Doheny, D., Manore, S.G., Wong, G.L., and Lo, H.W. (2020). Hedgehog Signaling and Truncated GLI1 in Cancer. Cells, 9.","DOI":"10.3390\/cells9092114"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1158\/2643-3230.BCD-20-0007","article-title":"Hedgehog Pathway Inhibitors: A New Therapeutic Class for the Treatment of Acute Myeloid Leukemia","volume":"1","author":"Jamieson","year":"2020","journal-title":"Blood Cancer Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e922","DOI":"10.1016\/S2352-3026(21)00270-2","article-title":"Harnessing the benefits of available targeted therapies in acute myeloid leukaemia","volume":"8","author":"Kantarjian","year":"2021","journal-title":"Lancet. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/S0140-6736(08)60457-2","article-title":"Acute lymphoblastic leukaemia","volume":"371","author":"Pui","year":"2008","journal-title":"Lancet."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bongiovanni, D., Saccomani, V., and Piovan, E. (2017). Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091904"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.3324\/haematol.2014.119248","article-title":"Hedgehog pathway mutations in T-cell acute lymphoblastic leukemia","volume":"100","author":"Dagklis","year":"2015","journal-title":"Haematologica."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1182\/blood-2016-03-703454","article-title":"Hedgehog pathway activation in T-cell acute lymphoblastic leukemia predicts response to SMO and GLI1 inhibitors","volume":"128","author":"Dagklis","year":"2016","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sigafoos, A.N., Paradise, B.D., and Fernandez-Zapico, M.E. (2021). Hedgehog\/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease. Cancers., 13.","DOI":"10.3390\/cancers13143410"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"188795","DOI":"10.1016\/j.bbcan.2022.188795","article-title":"Homeostases of epidermis and hair follicle, and development of basal cell carcinoma","volume":"1877","author":"Jaiswal","year":"2022","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1101\/gad.391106","article-title":"Hedgehog signaling and the retina: Insights into the mechanisms controlling the proliferative properties of neural precursors","volume":"20","author":"Locker","year":"2006","journal-title":"Genes. Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/cbf.3582","article-title":"The role of Shh signalling pathway in central nervous system development and related diseases","volume":"39","author":"Li","year":"2021","journal-title":"Cell Biochem. Funct."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10911-013-9291-7","article-title":"Hedgehog and Gli signaling in embryonic mammary gland development","volume":"18","author":"Lee","year":"2013","journal-title":"J. Mammary. Gland. Biol. Neoplasia."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1053\/j.gastro.2008.04.011","article-title":"Hedgehog signaling is required for effective regeneration of exocrine pancreas","volume":"135","author":"Fendrich","year":"2008","journal-title":"Gastroenterology."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, J., Lipinski, R.J., Gipp, J.J., Shaw, A.K., and Bushman, W. (2009). Hedgehog pathway responsiveness correlates with the presence of primary cilia on prostate stromal cells. BMC. Dev. Biol., 9.","DOI":"10.1186\/1471-213X-9-50"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nature01493","article-title":"Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer","volume":"422","author":"Watkins","year":"2003","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1111\/j.1524-475X.2008.00430.x","article-title":"Hedgehog signaling is essential for normal wound healing","volume":"16","author":"Le","year":"2008","journal-title":"Wound. Repair. Regen."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"944760","DOI":"10.3389\/fcell.2022.944760","article-title":"Hedgehog\/GLI signaling in hematopoietic development and acute myeloid leukemia-From bench to bedside","volume":"10","author":"Tesanovic","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17905","DOI":"10.1074\/jbc.R112.356006","article-title":"Hedgehog secretion and signal transduction in vertebrates","volume":"287","author":"Ryan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/s41586-019-1355-4","article-title":"Smoothened stimulation by membrane sterols drives Hedgehog pathway activity","volume":"571","author":"Deshpande","year":"2019","journal-title":"Nature"},{"key":"ref_23","first-page":"3041","article-title":"Primary cilia and their role in cancer","volume":"17","author":"Higgins","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.exphem.2016.08.009","article-title":"Primary cilia are present on human blood and bone marrow cells and mediate Hedgehog signaling","volume":"44","author":"Singh","year":"2016","journal-title":"Exp. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.tibs.2020.01.006","article-title":"Mechanistic Insights into the Generation and Transduction of Hedgehog Signaling","volume":"45","author":"Qi","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/13031","article-title":"Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1","volume":"1","author":"Kogerman","year":"1999","journal-title":"Nat. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1083\/jcb.201004108","article-title":"A mechanism for vertebrate Hedgehog signaling: Recruitment to cilia and dissociation of SuFu-Gli protein complexes","volume":"191","author":"Tukachinsky","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.ejca.2005.08.039","article-title":"GLI transcription factors: Mediators of oncogenic Hedgehog signalling","volume":"42","author":"Kasper","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10846","DOI":"10.1074\/jbc.M608599200","article-title":"A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome","volume":"282","author":"Pan","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.celrep.2013.12.003","article-title":"Gli protein activity is controlled by multisite phosphorylation in vertebrate Hedgehog signaling","volume":"6","author":"Niewiadomski","year":"2014","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eaah4117","DOI":"10.1126\/scisignal.aah4117","article-title":"The SCFbeta-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis","volume":"10","author":"Shimizu","year":"2017","journal-title":"Sci. Signal"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1128\/MCB.26.9.3365-3377.2006","article-title":"Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation","volume":"26","author":"Pan","year":"2006","journal-title":"Mol. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/384129a0","article-title":"The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog","volume":"384","author":"Stone","year":"1996","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/35077219","article-title":"The Hedgehog and Wnt signalling pathways in cancer","volume":"411","author":"Taipale","year":"2001","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/nature04117","article-title":"Vertebrate Smoothened functions at the primary cilium","volume":"437","author":"Corbit","year":"2005","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1126\/science.1139740","article-title":"Patched1 regulates hedgehog signaling at the primary cilium","volume":"317","author":"Rohatgi","year":"2007","journal-title":"Science."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1038\/s41467-019-10234-9","article-title":"Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm","volume":"10","author":"Qian","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chen, Y., Sasai, N., Ma, G., Yue, T., Jia, J., Briscoe, J., and Jiang, J. (2011). Sonic Hedgehog dependent phosphorylation by CK1alpha and GRK2 is required for ciliary accumulation and activation of smoothened. PLoS Biol., 9.","DOI":"10.1371\/journal.pbio.1001083"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1126\/science.1157983","article-title":"Beta-arrestin-mediated localization of smoothened to the primary cilium","volume":"320","author":"Kovacs","year":"2008","journal-title":"Science."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1083\/jcb.200907126","article-title":"Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium","volume":"187","author":"Milenkovic","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.devcel.2012.07.004","article-title":"A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia","volume":"23","author":"Dorn","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/cr.2012.134","article-title":"Smoothened transduces Hedgehog signal by forming a complex with Evc\/Evc2","volume":"22","author":"Yang","year":"2012","journal-title":"Cell Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1093\/hmg\/dds409","article-title":"The ciliary Evc\/Evc2 complex interacts with Smo and controls Hedgehog pathway activity in chondrocytes by regulating Sufu\/Gli3 dissociation and Gli3 trafficking in primary cilia","volume":"22","author":"Valencia","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1101\/gad.1902910","article-title":"The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins","volume":"24","author":"Humke","year":"2010","journal-title":"Genes. Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"556","DOI":"10.3389\/fgene.2019.00556","article-title":"Non-canonical Hedgehog Signaling Pathway in Cancer: Activation of GLI Transcription Factors Beyond Smoothened","volume":"10","author":"Pietrobono","year":"2019","journal-title":"Front. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/ng1196-353","article-title":"Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly","volume":"14","author":"Belloni","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/383407a0","article-title":"Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function","volume":"383","author":"Chiang","year":"1996","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1242\/dev.125.16.3123","article-title":"Evidence that preaxial polydactyly in the Doublefoot mutant is due to ectopic Indian Hedgehog signaling","volume":"125","author":"Yang","year":"1998","journal-title":"Development"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0092-8674(00)81268-4","article-title":"Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome","volume":"85","author":"Hahn","year":"1996","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1126\/science.272.5268.1668","article-title":"Human homolog of patched, a candidate gene for the basal cell nevus syndrome","volume":"272","author":"Johnson","year":"1996","journal-title":"Science."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1111\/ijd.15884","article-title":"Basal cell nevus syndrome: An update on clinical findings","volume":"61","author":"Fernandez","year":"2022","journal-title":"Int. J. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7555\/JBR.35.20210139","article-title":"Role of aberrant Sonic hedgehog signaling pathway in cancers and developmental anomalies","volume":"36","author":"Patel","year":"2021","journal-title":"J. Biomed. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9653244","DOI":"10.1155\/2022\/9653244","article-title":"Cancer Stem Cells: From an Insight into the Basics to Recent Advances and Therapeutic Targeting","volume":"2022","author":"Bisht","year":"2022","journal-title":"Stem. Cells Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"873","DOI":"10.2174\/156652409789105570","article-title":"Hedgehog target genes: Mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation","volume":"9","author":"Katoh","year":"2009","journal-title":"Curr. Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"960943","DOI":"10.3389\/fonc.2022.960943","article-title":"The hedgehog pathway in hematopoiesis and hematological malignancy","volume":"12","author":"Lemos","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.drudis.2021.12.005","article-title":"The Hedgehog pathway and its inhibitors: Emerging therapeutic approaches for basal cell carcinoma","volume":"27","author":"Jain","year":"2022","journal-title":"Drug. Discov. Today"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s10555-020-09860-3","article-title":"Signaling pathways in Rhabdomyosarcoma invasion and metastasis","volume":"39","author":"Ramadan","year":"2020","journal-title":"Cancer Metastasis. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"864035","DOI":"10.3389\/fcell.2022.864035","article-title":"Sonic Hedgehog Signaling in Cerebellar Development and Cancer","volume":"10","author":"Wang","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7969286","DOI":"10.1155\/2016\/7969286","article-title":"The Hedgehog Signaling Networks in Lung Cancer: The Mechanisms and Roles in Tumor Progression and Implications for Cancer Therapy","volume":"2016","author":"Abe","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cub.2006.11.033","article-title":"HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity","volume":"17","author":"Clement","year":"2007","journal-title":"Curr. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ydbio.2005.01.008","article-title":"Hedgehog signaling regulates expansion of pancreatic epithelial cells","volume":"280","author":"Kawahira","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/nature01972","article-title":"Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours","volume":"425","author":"Berman","year":"2003","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nature07275","article-title":"A paracrine requirement for hedgehog signalling in cancer","volume":"455","author":"Yauch","year":"2008","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4254","DOI":"10.1073\/pnas.0813203106","article-title":"Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis","volume":"106","author":"Tian","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1158\/0008-5472.CAN-07-5500","article-title":"Stroma-initiated hedgehog signaling takes center stage in B-cell lymphoma","volume":"68","author":"Lindemann","year":"2008","journal-title":"Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4048","DOI":"10.1073\/pnas.0611682104","article-title":"Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma","volume":"104","author":"Peacock","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1158\/0008-5472.CAN-07-6350","article-title":"Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas","volume":"68","author":"Becher","year":"2008","journal-title":"Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Suchors, C., and Kim, J. (2022). Canonical Hedgehog Pathway and Noncanonical GLI Transcription Factor Activation in Cancer. Cells, 11.","DOI":"10.3390\/cells11162523"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Whisenant, T.C., Ho, D.T., Benz, R.W., Rogers, J.S., Kaake, R.M., Gordon, E.A., Huang, L., Baldi, P., and Bardwell, L. (2010). Computational prediction and experimental verification of new MAP kinase docking sites and substrates including Gli transcription factors. PLoS Comput. Biol., 6.","DOI":"10.1371\/journal.pcbi.1000908"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bardwell, A.J., Wu, B., Sarin, K.Y., Waterman, M.L., Atwood, S.X., and Bardwell, L. (2022). ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1. Life Sci. Alliance, 5.","DOI":"10.26508\/lsa.202101353"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Peng, Z., Ji, Z., Mei, F., Lu, M., Ou, Y., and Cheng, X. (2013). Lithium inhibits tumorigenic potential of PDA cells through targeting hedgehog-GLI signaling pathway. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061457"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccr.2011.12.028","article-title":"The crosstalk of mTOR\/S6K1 and Hedgehog pathways","volume":"21","author":"Wang","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.cell.2008.02.047","article-title":"Application of active and kinase-deficient kinome collection for identification of kinases regulating hedgehog signaling","volume":"133","author":"Varjosalo","year":"2008","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7134","DOI":"10.18632\/oncotarget.6910","article-title":"DYRK1B as therapeutic target in Hedgehog\/GLI-dependent cancer cells with Smoothened inhibitor resistance","volume":"7","author":"Gruber","year":"2016","journal-title":"Oncotarget"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.1038\/sj.onc.1210991","article-title":"The EWS\/FLI1 oncogenic transcription factor deregulates GLI1","volume":"27","author":"Zwerner","year":"2008","journal-title":"Oncogene"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/978-1-4939-2772-2_13","article-title":"Determination of Acetylation of the Gli Transcription Factors","volume":"1322","author":"Coni","year":"2015","journal-title":"Methods. Mol. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2013","article-title":"Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation","volume":"12","author":"Canettieri","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"35494","DOI":"10.1074\/jbc.M114.595348","article-title":"The BET bromodomain inhibitor I-BET151 acts downstream of smoothened protein to abrogate the growth of hedgehog protein-driven cancers","volume":"289","author":"Long","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nm.3185","article-title":"Semaphorin 3d signaling defects are associated with anomalous pulmonary venous connections","volume":"19","author":"Degenhardt","year":"2013","journal-title":"Nat. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1158\/0008-5472.CAN-16-3315","article-title":"GLI1 Blockade Potentiates the Antitumor Activity of PI3K Antagonists in Lung Squamous Cell Carcinoma","volume":"77","author":"Kasiri","year":"2017","journal-title":"Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"51ra70","DOI":"10.1126\/scitranslmed.3001599","article-title":"Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma","volume":"2","author":"Buonamici","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8023","DOI":"10.1038\/ncomms9023","article-title":"Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1","volume":"6","author":"Schneider","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"108107","DOI":"10.1016\/j.pharmthera.2022.108107","article-title":"Targeting hedgehog signaling in pancreatic ductal adenocarcinoma","volume":"236","author":"Quatannens","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1101\/gad.1025302","article-title":"Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened","volume":"16","author":"Chen","year":"2002","journal-title":"Genes. Dev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1016\/j.bmcl.2009.08.049","article-title":"GDC-0449-a potent inhibitor of the hedgehog pathway","volume":"19","author":"Robarge","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1158\/1078-0432.CCR-12-1956","article-title":"Food and Drug Administration approval: Vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma","volume":"19","author":"Axelson","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1021\/ml1000307","article-title":"Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist","volume":"1","author":"Pan","year":"2010","journal-title":"ACS. Med. Chem. Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1158\/1078-0432.CCR-16-2051","article-title":"FDA Approval Summary: Sonidegib for Locally Advanced Basal Cell Carcinoma","volume":"23","author":"Casey","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1021\/ml2002423","article-title":"Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened","volume":"3","author":"Munchhof","year":"2012","journal-title":"ACS. Med. Chem. Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.1158\/1078-0432.CCR-19-0365","article-title":"FDA Approval Summary: Glasdegib for Newly Diagnosed Acute Myeloid Leukemia","volume":"25","author":"Norsworthy","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1126\/science.1171362","article-title":"Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer","volume":"324","author":"Olive","year":"2009","journal-title":"Science"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1007\/s12272-017-0987-x","article-title":"Development of taladegib as a sonic hedgehog signaling pathway inhibitor","volume":"40","author":"Jin","year":"2017","journal-title":"Arch. Pharm. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5507","DOI":"10.1016\/j.bmc.2012.07.034","article-title":"Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: Modification of the core skeleton for improved solubility","volume":"20","author":"Ohashi","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4103\/0976-500X.107628","article-title":"The dawn of hedgehog inhibitors: Vismodegib","volume":"4","author":"Sandhiya","year":"2013","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1056\/NEJMoa0905360","article-title":"Inhibition of the hedgehog pathway in advanced basal-cell carcinoma","volume":"361","author":"LoRusso","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrd3753","article-title":"Vismodegib","volume":"11","author":"Dlugosz","year":"2012","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1056\/NEJMoa1113713","article-title":"Efficacy and safety of vismodegib in advanced basal-cell carcinoma","volume":"366","author":"Sekulic","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1158\/1078-0432.CCR-10-2745","article-title":"Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors","volume":"17","author":"LoRusso","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13045-020-00929-8","article-title":"Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy","volume":"13","author":"Cortes","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1002\/ajh.25238","article-title":"Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results","volume":"93","author":"Cortes","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Chai, J.Y., Sugumar, V., Alshawsh, M.A., Wong, W.F., Arya, A., Chong, P.P., and Looi, C.Y. (2021). The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091188"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"8455","DOI":"10.1073\/pnas.0609699104","article-title":"Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists","volume":"104","author":"Lauth","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/10934529.2014.865425","article-title":"Synthesis and cytotoxicity studies of Hedgehog enzyme inhibitors SANT-1 and GANT-61 as anticancer agents","volume":"49","author":"Chenna","year":"2014","journal-title":"J. Environ. Sci. Health A Tox. Hazard. Subst. Environ. Eng."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Mullard, M., Cade, M., Morice, S., Dupuy, M., Danieau, G., Amiaud, J., Renault, S., Lezot, F., Brion, R., and Thepault, R.A. (2020). Sonic Hedgehog Signature in Pediatric Primary Bone Tumors: Effects of the GLI Antagonist GANT61 on Ewing\u2019s Sarcoma Tumor Growth. Cancers, 12.","DOI":"10.3390\/cancers12113438"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"E1038","DOI":"10.1073\/pnas.1114168109","article-title":"The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis","volume":"109","author":"Rajurkar","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s13402-020-00504-w","article-title":"The hedgehog pathway regulates cancer stem cells in serous adenocarcinoma of the ovary","volume":"43","author":"Sneha","year":"2020","journal-title":"Cell Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Lu, Y., Zhu, Y., Deng, S., Chen, Y., Li, W., Sun, J., and Xu, X. (2021). Targeting the Sonic Hedgehog Pathway to Suppress the Expression of the Cancer Stem Cell (CSC)-Related Transcription Factors and CSC-Driven Thyroid Tumor Growth. Cancers, 13.","DOI":"10.3390\/cancers13030418"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12943-016-0534-2","article-title":"Efficient elimination of pancreatic cancer stem cells by hedgehog\/GLI inhibitor GANT61 in combination with mTOR inhibition","volume":"15","author":"Miyazaki","year":"2016","journal-title":"Mol. Cancer"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"200","DOI":"10.15252\/embj.201489213","article-title":"Gli1\/DNA interaction is a druggable target for Hedgehog-dependent tumors","volume":"34","author":"Infante","year":"2015","journal-title":"EMBO J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"13432","DOI":"10.1073\/pnas.1006822107","article-title":"Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector","volume":"107","author":"Kim","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1172\/JCI42874","article-title":"Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog\/GLI pathway","volume":"121","author":"Beauchamp","year":"2011","journal-title":"J. Clin. Invest."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Chin, L., Kumana, C.R., Kwong, Y.L., and Gill, H. (2022). The Development and Clinical Applications of Oral Arsenic Trioxide for Acute Promyelocytic Leukaemia and Other Diseases. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091945"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1002\/cbin.11563","article-title":"Mechanistic effects of arsenic trioxide on acute promyelocytic leukemia and other types of leukemias","volume":"45","author":"Yousefnia","year":"2021","journal-title":"Cell Biol. Int."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1159\/000351603","article-title":"Arsenic trioxide inhibits the Hedgehog pathway which is aberrantly activated in acute promyelocytic leukemia","volume":"130","author":"Yang","year":"2013","journal-title":"Acta Haematol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1001\/jamadermatol.2015.5473","article-title":"Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma","volume":"152","author":"Ally","year":"2016","journal-title":"JAMA Dermatol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.ccr.2010.02.027","article-title":"Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth","volume":"17","author":"Kim","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Kenchegowda, M., Rahamathulla, M., Hani, U., Begum, M.Y., Guruswamy, S., Osmani, R.A.M., Gowrav, M.P., Alshehri, S., Ghoneim, M.M., and Alshlowi, A. (2021). Smart Nanocarriers as an Emerging Platform for Cancer Therapy: A Review. Molecules, 27.","DOI":"10.3390\/molecules27010146"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"121138","DOI":"10.1016\/j.biomaterials.2021.121138","article-title":"Polymeric nanomedicine for overcoming resistance mechanisms in hedgehog and Myc-amplified medulloblastoma","volume":"278","author":"Kumar","year":"2021","journal-title":"Biomaterials"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Singh, S.K., Gordetsky, J.B., Bae, S., Acosta, E.P., Lillard, J.W., and Singh, R. (2020). Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer. Cells, 9.","DOI":"10.3390\/cells9091976"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Poulaki, A., and Giannouli, S. (2021). Metabolic Swifts Govern Normal and Malignant B Cell Lymphopoiesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158269"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.exphem.2018.12.001","article-title":"From pluripotent stem cells to T cells","volume":"71","author":"Crooks","year":"2019","journal-title":"Exp. Hematol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41392-022-01058-z","article-title":"Natural killer cell homing and trafficking in tissues and tumors: From biology to application","volume":"7","author":"Ran","year":"2022","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1038\/leu.2011.143","article-title":"The controversial role of the Hedgehog pathway in normal and malignant hematopoiesis","volume":"25","author":"Mar","year":"2011","journal-title":"Leukemia"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.stem.2009.03.015","article-title":"Hedgehog signaling is dispensable for adult hematopoietic stem cell function","volume":"4","author":"Gao","year":"2009","journal-title":"Cell Stem. Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.stem.2009.03.016","article-title":"Hedgehog signaling is dispensable for adult murine hematopoietic stem cell function and hematopoiesis","volume":"4","author":"Hofmann","year":"2009","journal-title":"Cell Stem. Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.devcel.2005.01.010","article-title":"Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos","volume":"8","author":"Gering","year":"2005","journal-title":"Dev. Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2009-09-241703","article-title":"Gli1 regulates the proliferation and differentiation of HSCs and myeloid progenitors","volume":"115","author":"Merchant","year":"2010","journal-title":"Blood"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.stem.2009.05.006","article-title":"Smoothening the controversial role of hedgehog in hematopoiesis","volume":"4","author":"Merchant","year":"2009","journal-title":"Cell Stem. Cell"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1182\/blood-2007-02-075648","article-title":"The Hedgehog receptor Patched controls lymphoid lineage commitment","volume":"110","author":"Uhmann","year":"2007","journal-title":"Blood"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nri2151","article-title":"Sonic hedgehog signalling in T-cell development and activation","volume":"7","author":"Crompton","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Barbarulo, A., Lau, C.I., Mengrelis, K., Ross, S., Solanki, A., Saldana, J.I., and Crompton, T. (2016). Hedgehog Signalling in the Embryonic Mouse Thymus. J. Dev. Biol., 4.","DOI":"10.3390\/jdb4030022"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1073\/pnas.0809559106","article-title":"Characterization of the thymic IL-7 niche in vivo","volume":"106","author":"Alves","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"4017","DOI":"10.4049\/jimmunol.1302259","article-title":"An overview of the intrathymic intricacies of T cell development","volume":"192","author":"Shah","year":"2014","journal-title":"J. Immunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ajpath.2011.09.009","article-title":"Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms","volume":"180","author":"Ok","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"916","DOI":"10.4049\/jimmunol.2200214","article-title":"NPAT Supports CD8(+) Immature Single-Positive Thymocyte Proliferation and Thymic Development","volume":"209","author":"Cui","year":"2022","journal-title":"J. Immunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/0167-5699(93)90186-O","article-title":"Control points in early T-cell development","volume":"14","author":"Godfrey","year":"1993","journal-title":"Immunol. Today"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4049\/jimmunol.176.1.3","article-title":"Shaping the T cell repertoire","volume":"176","year":"2006","journal-title":"J. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.0105-2896.2006.00346.x","article-title":"Negative selection of the T-cell repertoire: Where and when does it occur?","volume":"209","author":"Kisielow","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0952-7915(99)80024-7","article-title":"Pleiotropic changes controlled by the pre-T-cell receptor","volume":"11","author":"Aifantis","year":"1999","journal-title":"Curr. Opin. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S1074-7613(00)80381-7","article-title":"Essential role of the pre-T cell receptor in allelic exclusion of the T cell receptor beta locus","volume":"7","author":"Aifantis","year":"1997","journal-title":"Immunity"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S1074-7613(00)80662-7","article-title":"On the role of the pre-T cell receptor in alphabeta versus gammadelta T lineage commitment","volume":"9","author":"Aifantis","year":"1998","journal-title":"Immunity"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev.immunol.14.1.73","article-title":"Cellular interactions in thymocyte development","volume":"14","author":"Anderson","year":"1996","journal-title":"Annu. Rev. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.it.2012.03.005","article-title":"Thymic epithelial cells: Working class heroes for T cell development and repertoire selection","volume":"33","author":"Anderson","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nri3667","article-title":"Positive and negative selection of the T cell repertoire: What thymocytes see (and don\u2019t see)","volume":"14","author":"Klein","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1084\/jem.178.1.257","article-title":"Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody","volume":"178","author":"Grabstein","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"9125","DOI":"10.1073\/pnas.90.19.9125","article-title":"Expression and function of the interleukin 7 receptor in murine lymphocytes","volume":"90","author":"Sudo","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/s41590-019-0479-x","article-title":"Flip the coin: IL-7 and IL-7R in health and disease","volume":"20","author":"Barata","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/1074-7613(95)90116-7","article-title":"Intrathymically expressed c-kit ligand (stem cell factor) is a major factor driving expansion of very immature thymocytes in vivo","volume":"3","author":"Rodewald","year":"1995","journal-title":"Immunity"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1084\/jem.20080829","article-title":"Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment","volume":"205","author":"Koch","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/nri1636","article-title":"Unique features of the pre-T-cell receptor alpha-chain: Not just a surrogate","volume":"5","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.4049\/jimmunol.161.8.3984","article-title":"Critical involvement of Tcf-1 in expansion of thymocytes","volume":"161","author":"Schilham","year":"1998","journal-title":"J. Immunol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1749-6632.2012.06626.x","article-title":"Differential requirements for Wnt and Notch signaling in hematopoietic versus thymic niches","volume":"1266","author":"Roozen","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/ni1234","article-title":"Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism","volume":"6","author":"Ciofani","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1177\/002215540305101115","article-title":"Expression of hedgehog proteins in the human thymus","volume":"51","author":"Sacedon","year":"2003","journal-title":"J. Histochem. Cytochem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S1074-7613(00)00019-4","article-title":"Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte","volume":"13","author":"Outram","year":"2000","journal-title":"Immunity"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.humpath.2010.12.023","article-title":"Glioma-associated oncogene homologue 3, a hedgehog transcription factor, is highly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma","volume":"42","author":"Greaves","year":"2011","journal-title":"Hum. Pathol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jaut.2015.12.004","article-title":"Sonic Hedgehog regulates thymic epithelial cell differentiation","volume":"68","author":"Saldana","year":"2016","journal-title":"J. Autoimmun."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1182\/blood-2008-03-144840","article-title":"Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation","volume":"113","author":"Outram","year":"2009","journal-title":"Blood"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/ni1313","article-title":"Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymus","volume":"7","author":"Graves","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"5144","DOI":"10.1182\/blood-2008-10-185751","article-title":"Sonic hedgehog negatively regulates pre-TCR-induced differentiation by a Gli2-dependent mechanism","volume":"113","author":"Rowbotham","year":"2009","journal-title":"Blood"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1182\/blood-2005-03-0998","article-title":"The transcription factor Gli3 regulates differentiation of fetal CD4- CD8- double-negative thymocytes","volume":"106","author":"Dessens","year":"2005","journal-title":"Blood"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.4049\/jimmunol.172.4.2296","article-title":"Reduced thymocyte development in sonic hedgehog knockout embryos","volume":"172","author":"Shah","year":"2004","journal-title":"J. Immunol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"4144","DOI":"10.4161\/cc.9.20.13453","article-title":"Non-redundant role for the transcription factor Gli1 at multiple stages of thymocyte development","volume":"9","author":"Drakopoulou","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1002\/eji.201141758","article-title":"Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte","volume":"42","author":"Furmanski","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3757","DOI":"10.1182\/blood-2006-07-037655","article-title":"Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation","volume":"109","author":"Rowbotham","year":"2007","journal-title":"Blood"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"904","DOI":"10.4161\/cc.7.7.5628","article-title":"Repression of hedgehog signal transduction in T-lineage cells increases TCR-induced activation and proliferation","volume":"7","author":"Rowbotham","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Solanki, A., Yanez, D.C., Ross, S., Lau, C.I., Papaioannou, E., Li, J., Saldana, J.I., and Crompton, T. (2018). Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of Shh. Development, 145.","DOI":"10.1242\/dev.146910"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.4161\/cc.4.9.1999","article-title":"Hedgehogs as negative regulators of the cell cycle","volume":"4","author":"Neumann","year":"2005","journal-title":"Cell Cycle"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1152\/physrev.00054.2006","article-title":"Hedgehog signaling in development and homeostasis of the gastrointestinal tract","volume":"87","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"5046","DOI":"10.4049\/jimmunol.173.8.5046","article-title":"Sonic hedgehog regulates early human thymocyte differentiation by counteracting the IL-7-induced development of CD34+ precursor cells","volume":"173","author":"Sacedon","year":"2004","journal-title":"J. Immunol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/nrc.2016.63","article-title":"The genetics and mechanisms of T cell acute lymphoblastic leukaemia","volume":"16","author":"Belver","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Malczewska, M., Kosmider, K., Bednarz, K., Ostapinska, K., Lejman, M., and Zawitkowska, J. (2022). Recent Advances in Treatment Options for Childhood Acute Lymphoblastic Leukemia. Cancers, 14.","DOI":"10.3390\/cancers14082021"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"841179","DOI":"10.3389\/fonc.2022.841179","article-title":"A Novel Risk Defining System for Pediatric T-Cell Acute Lymphoblastic Leukemia From CCCG-ALL-2015 Group","volume":"12","author":"Liu","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Qi, H.Z., Xu, J., Yang, Q.Q., Lin, R., Wang, Z.X., Zhao, K., Wang, Q., Zhou, X., Fan, Z.P., and Huang, F. (2022). Effect of pediatric- versus adult-type chemotherapy regimens on outcomes of allogeneic hematopoietic stem cell transplants for adult T-cell acute lymphoblastic leukemia in first complete remission. Bone Marrow Transplant.","DOI":"10.1038\/s41409-022-01796-2"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1056\/NEJMoa1110169","article-title":"Outcomes after induction failure in childhood acute lymphoblastic leukemia","volume":"366","author":"Schrappe","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"e29457","DOI":"10.1002\/pbc.29457","article-title":"Outcomes of children and young adults with T-cell acute lymphoblastic leukemia\/lymphoma who present in critical status","volume":"69","author":"Wayne","year":"2022","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Genesca, E., and Gonzalez-Gil, C. (2022). Latest Contributions of Genomics to T-Cell Acute Lymphoblastic Leukemia (T-ALL). Cancers, 14.","DOI":"10.3390\/cancers14102474"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Yang, K., and Zhang, H. (2022). Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?. Cancers, 14.","DOI":"10.3390\/cancers14225655"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Genesca, E., and la Starza, R. (2022). Early T-Cell Precursor ALL and Beyond: Immature and Ambiguous Lineage T-ALL Subsets. Cancers, 14.","DOI":"10.3390\/cancers14081873"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1535-6108(02)00018-1","article-title":"Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia","volume":"1","author":"Ferrando","year":"2002","journal-title":"Cancer Cell"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Bardelli, V., Arniani, S., Pierini, V., Di Giacomo, D., Pierini, T., Gorello, P., Mecucci, C., and La Starza, R. (2021). T-Cell Acute Lymphoblastic Leukemia: Biomarkers and Their Clinical Usefulness. Genes, 12.","DOI":"10.3390\/genes12081118"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Toribio, M.L., and Gonzalez-Garcia, S. (2023). Notch Partners in the Long Journey of T-ALL Pathogenesis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021383"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S1470-2045(08)70314-0","article-title":"Early T-cell precursor leukaemia: A subtype of very high-risk acute lymphoblastic leukaemia","volume":"10","author":"Mullighan","year":"2009","journal-title":"Lancet. Oncol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/nature10725","article-title":"The genetic basis of early T-cell precursor acute lymphoblastic leukaemia","volume":"481","author":"Zhang","year":"2012","journal-title":"Nature"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3324\/haematol.2011.051722","article-title":"Characterization of a pediatric T-cell acute lymphoblastic leukemia patient with simultaneous LYL1 and LMO2 rearrangements","volume":"97","author":"Homminga","year":"2012","journal-title":"Haematologica."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Summers, R.J., and Teachey, D.T. (2022). SOHO State of the Art Updates and Next Questions | Novel Approaches to Pediatric T-cell ALL and T-Lymphoblastic Lymphoma. Clin. Lymphoma Myeloma Leuk.","DOI":"10.1016\/j.clml.2022.07.010"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"934337","DOI":"10.3389\/fchem.2022.934337","article-title":"Key Considerations in Targeted Protein Degradation Drug Discovery and Development","volume":"10","author":"Qin","year":"2022","journal-title":"Front. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"784024","DOI":"10.3389\/fped.2021.784024","article-title":"Chimeric Antigen Receptor T-Cell Therapy in Paediatric B-Cell Precursor Acute Lymphoblastic Leukaemia: Curative Treatment Option or Bridge to Transplant?","volume":"9","author":"Buechner","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Newman, H., and Teachey, D.T. (2022). A Bright Horizon: Immunotherapy for Pediatric T-Cell Malignancies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158600"},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Abraham, A., and Matsui, W. (2021). Hedgehog Signaling in Myeloid Malignancies. Cancers, 13.","DOI":"10.3390\/cancers13194888"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41388-018-0431-9","article-title":"Hedgehog\/GLI1 activation leads to leukemic transformation of myelodysplastic syndrome in vivo and GLI1 inhibition results in antitumor activity","volume":"38","author":"Lau","year":"2019","journal-title":"Oncogene"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1158\/1078-0432.CCR-14-1059","article-title":"Expression of Hedgehog Pathway Mediator GLI Represents a Negative Prognostic Marker in Human Acute Myeloid Leukemia and Its Inhibition Exerts Antileukemic Effects","volume":"21","author":"Wellbrock","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1182\/blood-2016-05-718585","article-title":"GLI3 repressor determines Hedgehog pathway activation and is required for response to SMO antagonist glasdegib in AML","volume":"129","author":"Chaudhry","year":"2017","journal-title":"Blood"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13045-017-0396-0","article-title":"Hh\/Gli antagonist in acute myeloid leukemia with CBFA2T3-GLIS2 fusion gene","volume":"10","author":"Masetti","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/s41419-021-03504-2","article-title":"GLI1 reduces drug sensitivity by regulating cell cycle through PI3K\/AKT\/GSK3\/CDK pathway in acute myeloid leukemia","volume":"12","author":"Zhou","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"7477","DOI":"10.2147\/OTT.S216628","article-title":"Suppressing Hedgehog signaling reverses drug resistance of refractory acute myeloid leukemia","volume":"12","author":"Huang","year":"2019","journal-title":"Onco. Targets Ther."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1358\/dot.2019.55.9.3020160","article-title":"Glasdegib for the treatment of adult patients with newly diagnosed acute myeloid leukemia or high-grade myelodysplastic syndrome who are elderly or otherwise unfit for standard induction chemotherapy","volume":"55","author":"Goldsmith","year":"2019","journal-title":"Drugs. Today"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41419-021-03542-w","article-title":"Exovesicular-Shh confers Imatinib resistance by upregulating Bcl2 expression in chronic myeloid leukemia with variant chromosomes","volume":"12","author":"Anusha","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1182\/blood-2014-03-557298","article-title":"A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance","volume":"124","author":"Liu","year":"2014","journal-title":"Blood"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1182\/blood-2018-09-873695","article-title":"Activation of hedgehog signaling associates with early disease progression in chronic lymphocytic leukemia","volume":"133","author":"Ghia","year":"2019","journal-title":"Blood"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.leukres.2012.06.014","article-title":"Defining causative factors contributing in the activation of hedgehog signaling in diffuse large B-cell lymphoma","volume":"36","author":"Ramirez","year":"2012","journal-title":"Leuk. Res."},{"key":"ref_202","first-page":"4629","article-title":"Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells","volume":"29","author":"Kawahara","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_203","first-page":"893","article-title":"Effects of combination of notch inhibitor plus hedgehog inhibitor or Wnt inhibitor on growth of leukemia cells","volume":"31","author":"Okuhashi","year":"2011","journal-title":"Anticancer Res."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nature06225","article-title":"Hedgehog regulates smoothened activity by inducing a conformational switch","volume":"450","author":"Zhao","year":"2007","journal-title":"Nature"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1086\/302557","article-title":"The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A\/B.; No phenotype prediction from the position of GLI3 mutations","volume":"65","author":"Radhakrishna","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1038\/s41375-018-0097-x","article-title":"Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia","volume":"32","author":"Burns","year":"2018","journal-title":"Leukemia"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/ng.3909","article-title":"The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia","volume":"49","author":"Liu","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Martelli, A.M., Paganelli, F., Fazio, A., Bazzichetto, C., Conciatori, F., and McCubrey, J.A. (2019). The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response. Cancers, 11.","DOI":"10.3390\/cancers11050629"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Kosmider, K., Karska, K., Kozakiewicz, A., Lejman, M., and Zawitkowska, J. (2022). Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The State-of-the-Art Knowledge and Future Prospects. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073795"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1158\/1535-7163.MCT-06-0076","article-title":"Synergistic induction of apoptosis in human leukemia T cells by the Akt inhibitor perifosine and etoposide through activation of intrinsic and Fas-mediated extrinsic cell death pathways","volume":"5","author":"Nyakern","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/leu.2008.79","article-title":"The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute leukemia cells by a JNK-dependent mechanism","volume":"22","author":"Chiarini","year":"2008","journal-title":"Leukemia"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.biochi.2013.12.019","article-title":"Inhibition of hedgehog signaling by GANT58 induces apoptosis and shows synergistic antitumor activity with AKT inhibitor in acute T cell leukemia cells","volume":"101","author":"Hou","year":"2014","journal-title":"Biochimie"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/nm.3328","article-title":"Coordinate activation of Shh and PI3K signaling in PTEN-deficient glioblastoma: New therapeutic opportunities","volume":"19","author":"Filbin","year":"2013","journal-title":"Nat. Med."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"5895","DOI":"10.1073\/pnas.0700776104","article-title":"Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK\/AKT pathways","volume":"104","author":"Stecca","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"638","DOI":"10.18632\/oncotarget.310","article-title":"The GLI genes as the molecular switch in disrupting Hedgehog signaling in colon cancer","volume":"2","author":"Mazumdar","year":"2011","journal-title":"Oncotarget"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"14048","DOI":"10.1074\/jbc.M611089200","article-title":"Oncogenic KRAS activates hedgehog signaling pathway in pancreatic cancer cells","volume":"282","author":"Ji","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1158\/0008-5472.CAN-08-1808","article-title":"Sonic hedgehog signaling pathway is activated in ALK-positive anaplastic large cell lymphoma","volume":"69","author":"Singh","year":"2009","journal-title":"Cancer Res."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"6557","DOI":"10.1038\/s41598-017-06370-1","article-title":"The regulation of Hh\/Gli1 signaling cascade involves Gsk3beta- mediated mechanism in estrogen-derived endometrial hyperplasia","volume":"7","author":"Kaushal","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_219","doi-asserted-by":"crossref","unstructured":"Martelli, A.M., Paganelli, F., Evangelisti, C., Chiarini, F., and McCubrey, J.A. (2022). Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies. Cells, 11.","DOI":"10.3390\/cells11111812"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"12471","DOI":"10.18632\/oncotarget.22527","article-title":"Research progress on the forkhead box C1","volume":"9","author":"Wang","year":"2018","journal-title":"Oncotarget"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"721959","DOI":"10.3389\/fonc.2021.721959","article-title":"Therapeutically Targeting Cancers That Overexpress FOXC1: A Transcriptional Driver of Cell Plasticity, Partial EMT, and Cancer Metastasis","volume":"11","author":"Ray","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/s41375-020-0999-2","article-title":"Cross-talk between GLI transcription factors and FOXC1 promotes T-cell acute lymphoblastic leukemia dissemination","volume":"35","author":"Tosello","year":"2021","journal-title":"Leukemia"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/onc.2012.544","article-title":"MEK1-RSK2 contributes to Hedgehog signaling by stabilizing GLI2 transcription factor and inhibiting ubiquitination","volume":"33","author":"Liu","year":"2014","journal-title":"Oncogene"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.celrep.2015.09.063","article-title":"FOXC1 Activates Smoothened-Independent Hedgehog Signaling in Basal-like Breast Cancer","volume":"13","author":"Han","year":"2015","journal-title":"Cell Rep."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1182\/blood-2016-09-692582","article-title":"The NOTCH1-MYC highway toward T-cell acute lymphoblastic leukemia","volume":"129","author":"Ferrando","year":"2017","journal-title":"Blood"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"e350","DOI":"10.1038\/bcj.2015.80","article-title":"A Phase 1 study of the novel gamma-secretase inhibitor PF-03084014 in patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma","volume":"5","author":"Papayannidis","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/978-3-319-89512-3_18","article-title":"Notch in Leukemia","volume":"1066","author":"McCarter","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"6544","DOI":"10.1038\/s41388-020-01453-2","article-title":"Crosstalk between Hedgehog pathway and the glucocorticoid receptor pathway as a basis for combination therapy in T-cell acute lymphoblastic leukemia","volume":"39","author":"Bongiovanni","year":"2020","journal-title":"Oncogene"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1182\/blood-2011-03-338707","article-title":"Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: Results of the AIEOP-BFM-ALL 2000 study","volume":"118","author":"Schrappe","year":"2011","journal-title":"Blood"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"44079","DOI":"10.1038\/srep44079","article-title":"Selective targeting of HDAC1\/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma","volume":"7","author":"Coni","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.mce.2007.07.003","article-title":"Crosstalk between the glucocorticoid receptor and other transcription factors: Molecular aspects","volume":"275","author":"Kassel","year":"2007","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1182\/blood-2006-12-060970","article-title":"Low-dose arsenic trioxide sensitizes glucocorticoid-resistant acute lymphoblastic leukemia cells to dexamethasone via an Akt-dependent pathway","volume":"110","author":"Bornhauser","year":"2007","journal-title":"Blood"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.celrep.2015.06.054","article-title":"AMP-Activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma","volume":"12","author":"Li","year":"2015","journal-title":"Cell Rep."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"49869","DOI":"10.18632\/oncotarget.17769","article-title":"Dual degradation signals destruct GLI1: AMPK inhibits GLI1 through beta-TrCP-mediated proteasome degradation","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"188785","DOI":"10.1016\/j.bbcan.2022.188785","article-title":"AMPK: An odyssey of a metabolic regulator, a tumor suppressor, and now a contextual oncogene","volume":"1877","author":"Penugurti","year":"2022","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/leu.2011.269","article-title":"AMP-dependent kinase\/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia: Therapeutic implications","volume":"26","author":"Grimaldi","year":"2012","journal-title":"Leukemia"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cmet.2016.03.008","article-title":"AMPK Is Essential to Balance Glycolysis and Mitochondrial Metabolism to Control T-ALL Cell Stress and Survival","volume":"23","author":"Kishton","year":"2016","journal-title":"Cell Metab."},{"key":"ref_238","doi-asserted-by":"crossref","unstructured":"Tosello, V., Bongiovanni, D., Di Martino, L., Franchin, C., Zanovello, P., Arrigoni, G., and Piovan, E. (2021). Responsiveness to Hedgehog Pathway Inhibitors in T-Cell Acute Lymphoblastic Leukemia Cells Is Highly Dependent on 5\u2019AMP-Activated Kinase Inactivation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126384"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"9538","DOI":"10.18632\/oncotarget.7070","article-title":"The energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint","volume":"7","author":"Basile","year":"2016","journal-title":"Oncotarget"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1093\/carcin\/bgs404","article-title":"Down-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development","volume":"34","author":"Santos","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"e29926","DOI":"10.1002\/pbc.29926","article-title":"Diverse mutations and structural variations contribute to Notch signaling deregulation in paediatric T-cell lymphoblastic lymphoma","volume":"69","author":"Balague","year":"2022","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11912-021-01168-x","article-title":"Lymphoblastic Lymphoma: A Concise Review","volume":"24","author":"Intermesoli","year":"2022","journal-title":"Curr. Oncol. Rep."},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Kyriakidis, I., Kyriakidis, K., and Tsezou, A. (2022). MicroRNAs and the Diagnosis of Childhood Acute Lymphoblastic Leukemia: Systematic Review, Meta-Analysis and Re-Analysis with Novel Small RNA-Seq Tools. Cancers, 14.","DOI":"10.3390\/cancers14163976"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.semcdb.2021.04.002","article-title":"Regulation of cell signaling pathways by circular RNAs and microRNAs in different cancers: Spotlight on Wnt\/beta-catenin, JAK\/STAT, TGF\/SMAD, SHH\/GLI, NOTCH and Hippo pathways","volume":"124","author":"Farooqi","year":"2022","journal-title":"Semin Cell Dev. Biol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s12032-022-01710-2","article-title":"The crosstalk between long non-coding RNAs and the hedgehog signaling pathway in cancer","volume":"39","author":"Sargazi","year":"2022","journal-title":"Med. Oncol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"113507","DOI":"10.1016\/j.biopha.2022.113507","article-title":"Role of hedgehog signaling related non-coding RNAs in developmental and pathological conditions","volume":"153","author":"HajiEsmailPoor","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/ijc.33527","article-title":"Deleterious point mutations in T-cell acute lymphoblastic leukemia: Mechanistic insights into leukemogenesis","volume":"149","author":"Roy","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1084\/jem.183.5.2283","article-title":"Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles","volume":"183","author":"Pear","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.immuni.2010.01.004","article-title":"Notch signaling in the immune system","volume":"32","author":"Radtke","year":"2010","journal-title":"Immunity"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1182\/blood-2014-04-566687","article-title":"JAK3 mutants transform hematopoietic cells through JAK1 activation, causing T-cell acute lymphoblastic leukemia in a mouse model","volume":"124","author":"Degryse","year":"2014","journal-title":"Blood"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cellsig.2017.06.011","article-title":"From the outside, from within: Biological and therapeutic relevance of signal transduction in T-cell acute lymphoblastic leukemia","volume":"38","author":"Oliveira","year":"2017","journal-title":"Cell Signal"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/sj.leu.2404546","article-title":"NOTCH1-induced T-cell leukemia in transgenic zebrafish","volume":"21","author":"Chen","year":"2007","journal-title":"Leukemia"},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"Koudijs, M.J., den Broeder, M.J., Keijser, A., Wienholds, E., Houwing, S., van Rooijen, E.M., Geisler, R., and van Eeden, F.J. (2005). The zebrafish mutants dre, uki, and lep encode negative regulators of the hedgehog signaling pathway. PLoS Genet., 1.","DOI":"10.1371\/journal.pgen.0010019"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ccr.2004.08.019","article-title":"Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+\/-)p53(-\/-) mice","volume":"6","author":"Romer","year":"2004","journal-title":"Cancer Cell"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature13283","article-title":"The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation","volume":"511","author":"Zahreddine","year":"2014","journal-title":"Nature"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"37370","DOI":"10.1074\/jbc.M703697200","article-title":"Protein kinase A, not Epac, suppresses hedgehog activity and regulates glucocorticoid sensitivity in acute lymphoblastic leukemia cells","volume":"282","author":"Ji","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1038\/s41388-021-01783-9","article-title":"Targeting non-canonical activation of GLI1 by the SOX2-BRD4 transcriptional complex improves the efficacy of HEDGEHOG pathway inhibition in melanoma","volume":"40","author":"Pietrobono","year":"2021","journal-title":"Oncogene"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2962\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:23:01Z","timestamp":1760120581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,3]]},"references-count":258,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032962"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032962","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,3]]}}}