{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:00:17Z","timestamp":1792040417994,"version":"4.4.0"},"reference-count":151,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"crossref","award":["FAR 2024"],"award-info":[{"award-number":["FAR 2024"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"crossref","award":["FAR 2025"],"award-info":[{"award-number":["FAR 2025"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondazione Di Bella"},{"name":"Associazione Gli Onconauti"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acute Lymphoblastic Leukemia (ALL) is a heterogeneous hematological malignancy in which disease progression and response to therapy are influenced by a complex network of molecular alterations, interactions with the bone marrow microenvironment, and epigenetic modulation mechanisms. Crosstalk between oncogenic, inflammatory, and immunoregulatory signaling pathways, together with epigenetic modifications, contributes to the maintenance of leukemic survival and the development of therapeutic resistance. This review analyzes the role of cytokines and chemokines such as IL-6, TNF-\u03b1, and CXCL12, which act as biological biomarkers and key mediators of leukemia niche remodeling, and the main signaling pathways involved in ALL, such as Wnt\/\u03b2-catenin, JAK\/STAT, PI3K\/AKT\/mTOR, Notch, and BCR, highlighting their functional interconnection with the tumor microenvironment. The role of epigenetics in modulating the dialogue between leukemia cells and stromal components is also discussed. Epigenetic programs govern leukemia\u2019s dependence on stromal support, inflammatory and niche-derived signals, as well as the microenvironment signaling pathways. Overall, targeting leukemia-niche interactions is a crucial strategy for improving outcomes in ALL and to identify potential molecular vulnerabilities, also for developing new therapeutic approaches for the treatment of the disease.<\/jats:p>","DOI":"10.3390\/cells15050467","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:52:11Z","timestamp":1772711531000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cytokines, Signaling and Epigenetic Mechanisms: Shaping the Acute Lymphoblastic Leukemia Microenvironment"],"prefix":"10.3390","volume":"15","author":[{"given":"Carolina","family":"Simioni","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Laboratory for Technologies of Advanced Therapies (LTTA)-Electron Microscopy Center, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-1477","authenticated-orcid":false,"given":"Luca Maria","family":"Neri","sequence":"additional","affiliation":[{"name":"Laboratory for Technologies of Advanced Therapies (LTTA)-Electron Microscopy Center, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hu, C., Chen, W., Zhang, P., Shen, T., and Xu, M. (2025). Global, regional, and national burden of leukemia: Epidemiological trends analysis from 1990 to 2021. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0325937"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1038\/s12276-024-01335-7","article-title":"Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)","volume":"56","author":"Lyu","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1158\/1055-9965.EPI-22-1227","article-title":"Incidence and Mortality Rates for Childhood Acute Lymphoblastic Leukemia in Puerto Rican Hispanics, 2012\u20132016","volume":"32","author":"Suarez","year":"2023","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e577","DOI":"10.1038\/bcj.2017.53","article-title":"Acute lymphoblastic leukemia: A comprehensive review and 2017 update","volume":"7","author":"Terwilliger","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1002\/ajh.27708","article-title":"Adult Acute Lymphoblastic Leukemia: 2025 Update on Diagnosis, Therapy, and Monitoring","volume":"100","author":"Kantarjian","year":"2025","journal-title":"Am. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hanifiha, M., Ghanbari, A., Keykhaei, M., Saeedi Moghaddam, S., Rezaei, N., Pasha Zanous, M., Yoosefi, M., Ghasemi, E., Rezaei, N., and Shahin, S. (2022). Global, regional, and national burden and quality of care index in children and adolescents: A systematic analysis for the global burden of disease study 1990\u20132017. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267596"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1002\/cncr.30899","article-title":"Survival among children diagnosed with acute lymphoblastic leukemia in the United States, by race and age, 2001 to 2009: Findings from the CONCORD-2 study","volume":"123","author":"Tai","year":"2017","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/ejh.13247","article-title":"Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry","volume":"103","author":"Lennmyr","year":"2019","journal-title":"Eur. J. Haematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1182\/blood.2023022919","article-title":"Genetic subtypes of B-cell acute lymphoblastic leukemia in adults","volume":"145","author":"Passet","year":"2025","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149730","DOI":"10.1016\/j.gene.2025.149730","article-title":"Mechanisms and clinical implications of microRNA associations and signaling pathways in B-cell acute lymphoblastic leukemia","volume":"967","author":"Dhiflaoui","year":"2025","journal-title":"Gene"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1097\/HS9.0000000000000053","article-title":"Advances in B-cell Precursor Acute Lymphoblastic Leukemia Genomics","volume":"2","author":"Schwab","year":"2018","journal-title":"Hemasphere"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/s41375-025-02599-2","article-title":"T-cell acute lymphoblastic leukaemia: Subtype prevalence, clinical outcome, and emerging targeted treatments","volume":"39","author":"Buckley","year":"2025","journal-title":"Leukemia"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sin, C.F., and Man, P.M. (2021). Early T-Cell Precursor Acute Lymphoblastic Leukemia: Diagnosis, Updates in Molecular Pathogenesis, Management, and Novel Therapies. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.750789"},{"key":"ref_14","first-page":"1164","article-title":"The bone marrow microenvironment as a mediator of chemoresistance in acute lymphoblastic leukemia","volume":"2","author":"Meyer","year":"2019","journal-title":"Cancer Drug Resist."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nature12984","article-title":"The bone marrow niche for haematopoietic stem cells","volume":"505","author":"Morrison","year":"2014","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41568-020-0245-2","article-title":"Bone marrow niches in haematological malignancies","volume":"20","author":"Bonnet","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","first-page":"346","article-title":"Recent advances in acute lymphoblastic leukemia","volume":"25","author":"Pui","year":"2011","journal-title":"Oncology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41392-023-01480-x","article-title":"Epigenetic regulation in the tumor microenvironment: Molecular mechanisms and therapeutic targets","volume":"8","author":"Yang","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dander, E., Palmi, C., D\u2019Amico, G., and Cazzaniga, G. (2021). The Bone Marrow Niche in B-Cell Acute Lymphoblastic Leukemia: The Role of Microenvironment from Pre-Leukemia to Overt Leukemia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094426"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hughes, A.M., Kuek, V., Kotecha, R.S., and Cheung, L.C. (2022). The Bone Marrow Microenvironment in B-Cell Development and Malignancy. Cancers, 14.","DOI":"10.3390\/cancers14092089"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1186\/s12967-024-05900-6","article-title":"Cellular crosstalk in the bone marrow niche","volume":"22","author":"Huang","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Delahaye, M.C., Salem, K.I., Pelletier, J., Aurrand-Lions, M., and Mancini, S.J.C. (2020). Toward Therapeutic Targeting of Bone Marrow Leukemic Niche Protective Signals in B-Cell Acute Lymphoblastic Leukemia. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.606540"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Marchand, T., and Pinho, S. (2021). Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.775128"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40164-021-00233-2","article-title":"Leukemia stem cell-bone marrow microenvironment interplay in acute myeloid leukemia development","volume":"10","author":"Yao","year":"2021","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.ccell.2015.05.002","article-title":"CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance","volume":"27","author":"Pitt","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nature19801","article-title":"T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments","volume":"538","author":"Hawkins","year":"2016","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Petit, C., Gouel, F., Dubus, I., Heuclin, C., Roget, K., and Vannier, J.P. (2016). Hypoxia promotes chemoresistance in acute lymphoblastic leukemia cell lines by modulating death signaling pathways. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2776-1"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bruno, S., Mancini, M., De Santis, S., Monaldi, C., Cavo, M., and Soverini, S. (2021). The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136857"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e40273","DOI":"10.1097\/MD.0000000000040273","article-title":"Central role of hypoxia-inducible factor-1alpha in metabolic reprogramming of cancer cells: A review","volume":"103","author":"Zhu","year":"2024","journal-title":"Medicine"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Jimenez-Morales, S., Aranda-Uribe, I.S., Perez-Amado, C.J., Ramirez-Bello, J., and Hidalgo-Miranda, A. (2021). Mechanisms of Immunosuppressive Tumor Evasion: Focus on Acute Lymphoblastic Leukemia. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.737340"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101669","DOI":"10.1016\/j.bonr.2023.101669","article-title":"Metabolic crosstalk between stromal and malignant cells in the bone marrow niche","volume":"18","author":"Tirado","year":"2023","journal-title":"Bone Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Simioni, C., Conti, I., Varano, G., Brenna, C., Costanzi, E., and Neri, L.M. (2021). The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.673506"},{"key":"ref_33","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_34","doi-asserted-by":"crossref","unstructured":"Drozak, P., Brylinski, L., and Zawitkowska, J. (2022). A Comprehensive Overview of Recent Advances in Epigenetics in Pediatric Acute Lymphoblastic Leukemia. Cancers, 14.","DOI":"10.3390\/cancers14215384"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Xu, H., Yu, H., Jin, R., Wu, X., and Chen, H. (2021). Genetic and Epigenetic Targeting Therapy for Pediatric Acute Lymphoblastic Leukemia. Cells, 10.","DOI":"10.3390\/cells10123349"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3349\/ymj.2009.50.4.455","article-title":"Epigenetic cross-talk between DNA methylation and histone modifications in human cancers","volume":"50","author":"Kondo","year":"2009","journal-title":"Yonsei Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tang, J., Ye, X., Xu, Z., Min, T., Tian, Z., Ma, L., He, Y., and Jiang, B. (2025). Epigenetic mechanisms of drug resistance in acute myeloid leukemia: Advances in small-molecule targeted therapy. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1672524"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"r105","DOI":"10.1186\/gb-2013-14-9-r105","article-title":"Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia","volume":"14","author":"Nordlund","year":"2013","journal-title":"Genome Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1200\/JCO.2008.19.3441","article-title":"Epigenetic regulation of microRNAs in acute lymphoblastic leukemia","volume":"27","author":"Agirre","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Abdollahzadeh, B., Cantale Aeo, N.M., Giordano, N., Orlando, A., Basciani, M., Peruzzi, G., Grazioli, P., Screpanti, I., Felli, M.P., and Campese, A.F. (2024). The NF-kappaB1\/p50 Subunit Influences the Notch\/IL-6-Driven Expansion of Myeloid-Derived Suppressor Cells in Murine T-Cell Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25189882"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrclinonc.2018.8","article-title":"Targeting the IL-6\/JAK\/STAT3 signalling axis in cancer","volume":"15","author":"Johnson","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1365-3083.2006.01750.x","article-title":"Interleukin-6 trans-signalling in chronic inflammation and cancer","volume":"63","author":"Scheller","year":"2006","journal-title":"Scand. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"156267","DOI":"10.1016\/j.cyto.2023.156267","article-title":"Cytokine network imbalance in children with B-cell acute lymphoblastic leukemia at diagnosis","volume":"169","author":"Dai","year":"2023","journal-title":"Cytokine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12032-024-02547-7","article-title":"Dual roles of extracellular vesicles in acute lymphoblastic leukemia: Implications for disease progression and theranostic strategies","volume":"42","author":"Lajevardi","year":"2024","journal-title":"Med. Oncol."},{"key":"ref_45","first-page":"158","article-title":"IL-7 receptor expression is frequent in T-cell acute lymphoblastic leukemia and predicts sensitivity to JAK inhibition","volume":"142","author":"Courtois","year":"2023","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1080\/10428190400027852","article-title":"Interleukin-7 in T-cell acute lymphoblastic leukemia: An extrinsic factor supporting leukemogenesis?","volume":"46","author":"Barata","year":"2005","journal-title":"Leuk. Lymphoma"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1182\/bloodadvances.2018021063","article-title":"STAT5 is essential for IL-7-mediated viability, growth, and proliferation of T-cell acute lymphoblastic leukemia cells","volume":"2","author":"Ribeiro","year":"2018","journal-title":"Blood Adv."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1038\/leu.2016.83","article-title":"MEK and PI3K-AKT inhibitors synergistically block activated IL7 receptor signaling in T-cell acute lymphoblastic leukemia","volume":"30","author":"Uitdehaag","year":"2016","journal-title":"Leukemia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1038\/s41375-025-02734-z","article-title":"Distinct stromal cell populations define the B-cell acute lymphoblastic leukemia microenvironment","volume":"39","author":"Kazybay","year":"2025","journal-title":"Leukemia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1182\/blood.2023019721","article-title":"IL-7 receptor signaling drives human B-cell progenitor differentiation and expansion","volume":"142","author":"Kaiser","year":"2023","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7357","DOI":"10.1038\/s41388-019-0921-4","article-title":"T-cell acute lymphoblastic leukemia displays autocrine production of Interleukin-7","volume":"38","author":"Buffiere","year":"2019","journal-title":"Oncogene"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1111\/bjh.12205","article-title":"MLL-rearranged acute lymphoblastic leukaemia stem cell interactions with bone marrow stroma promote survival and therapeutic resistance that can be overcome with CXCR4 antagonism","volume":"160","author":"Sison","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Mukaida, N., Tanabe, Y., and Baba, T. (2017). Chemokines as a Conductor of Bone Marrow Microenvironment in Chronic Myeloid Leukemia. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081824"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.7150\/ijbs.82317","article-title":"CXCL12-CXCR4\/CXCR7 Axis in Cancer: From Mechanisms to Clinical Applications","volume":"19","author":"Yang","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/nm1075","article-title":"Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1","volume":"10","author":"Ceradini","year":"2004","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cyto.2010.06.006","article-title":"CXCL12 gene expression is upregulated by hypoxia and growth arrest but not by inflammatory cytokines in rheumatoid synovial fibroblasts","volume":"53","author":"Santiago","year":"2011","journal-title":"Cytokine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cytogfr.2023.10.003","article-title":"An emerging paradigm of CXCL12 involvement in the metastatic cascade","volume":"75","author":"Anastasiadou","year":"2024","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1007\/s00277-025-06237-w","article-title":"Tumor microenvironment as a novel therapeutic target for lymphoid leukemias","volume":"104","author":"Mousavi","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.exphem.2016.10.005","article-title":"Tumor necrosis factor alpha in the onset and progression of leukemia","volume":"45","author":"Zhou","year":"2017","journal-title":"Exp. Hematol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Saluja, S., Bansal, I., Bhardwaj, R., Beg, M.S., and Palanichamy, J.K. (2024). Inflammation as a driver of hematological malignancies. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1347402"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"D\u2019Amico, G., Starace, R., Della Lastra, M., Marimpietri, D., Dander, E., Morandi, F., and Airoldi, I. (2025). Dysregulation of the Bone Marrow Microenvironment in Pediatric Tumors: The Role of Extracellular Vesicles in Acute Leukemias and Neuroblastoma. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115380"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/10245330701340759","article-title":"Angiogenesis factor pattern differs in acute lymphoblastic leukemia and chronic lymphocytic leukemia","volume":"12","author":"Aref","year":"2007","journal-title":"Hematology"},{"key":"ref_63","first-page":"e24835","article-title":"Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance","volume":"14","author":"Verma","year":"2022","journal-title":"Cureus"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1056\/NEJMp048121","article-title":"TGF-beta signaling, tumor suppression, and acute lymphoblastic leukemia","volume":"351","author":"Downing","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Rodrigues-Junior, D.M., Tsirigoti, C., Lim, S.K., Heldin, C.H., and Moustakas, A. (2022). Extracellular Vesicles and Transforming Growth Factor beta Signaling in Cancer. Front. Cell. Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.849938"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Liu, X., Wei, Q., Lu, L., Cui, S., Ma, K., Zhang, W., Ma, F., Li, H., Fu, X., and Zhang, C. (2023). Immunomodulatory potential of mesenchymal stem cell-derived extracellular vesicles: Targeting immune cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1094685"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"104241","DOI":"10.1016\/j.labinv.2025.104241","article-title":"Combined Multicolor Immunofluorescence Staining and Spatial In Situ messenger RNA Expression Analysis Identifies Potential Fibrosis Drivers in Acute Lymphoblastic Leukemia","volume":"105","author":"Braunig","year":"2025","journal-title":"Lab. Invest."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Hurwitz, S., Lee, K.J., Fourfouris, T., Choi, I., Parikh, K., Friedmann, R., Zarrabi, M., and Kim, Y.M. (2025). Targeting Wnt Signaling in Acute Lymphoblastic Leukemia. Cancers, 17.","DOI":"10.3390\/cancers17152456"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5413","DOI":"10.1002\/jcp.29429","article-title":"Targeting Wnt\/beta-catenin and PI3K\/Akt\/mTOR pathways in T-cell acute lymphoblastic leukemia","volume":"235","author":"Evangelisti","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Chiarini, F., Paganelli, F., Martelli, A.M., and Evangelisti, C. (2020). The Role Played by Wnt\/beta-Catenin Signaling Pathway in Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031098"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.cell.2012.05.012","article-title":"Wnt\/beta-catenin signaling and disease","volume":"149","author":"Clevers","year":"2012","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1053\/j.seminhematol.2008.09.008","article-title":"Epigenetics of acute lymphocytic leukemia","volume":"46","author":"Yang","year":"2009","journal-title":"Semin. Hematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s00005-020-00583-5","article-title":"WNT7A Expression is Downregulated in T Lymphocytes after T-Cell Receptor Activation Due to Histone Modifications and in T-ALL by DNA Methylation","volume":"68","year":"2020","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Fasouli, E.S., and Katsantoni, E. (2021). JAK-STAT in Early Hematopoiesis and Leukemia. Front. Cell. Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.669363"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.coi.2012.01.015","article-title":"The role of STAT5 in lymphocyte development and transformation","volume":"24","author":"Farrar","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.coi.2010.02.004","article-title":"STAT5 in B cell development and leukemia","volume":"22","author":"Malin","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Fattizzo, B., Rosa, J., Giannotta, J.A., Baldini, L., and Fracchiolla, N.S. (2020). The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00273"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1182\/blood-2014-06-580480","article-title":"Efficacy of JAK\/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia","volume":"125","author":"Maude","year":"2015","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9414","DOI":"10.1073\/pnas.0811761106","article-title":"JAK mutations in high-risk childhood acute lymphoblastic leukemia","volume":"106","author":"Mullighan","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7347","DOI":"10.1158\/0008-5472.CAN-10-1528","article-title":"CRLF2 and JAK2 in B-progenitor acute lymphoblastic leukemia: A novel association in oncogenesis","volume":"70","author":"Roll","year":"2010","journal-title":"Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1084\/jem.20040789","article-title":"Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells","volume":"200","author":"Barata","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Simioni, C., Martelli, A.M., Zauli, G., Melloni, E., and Neri, L.M. (2019). Targeting mTOR in Acute Lymphoblastic Leukemia. Cells, 8.","DOI":"10.3390\/cells8020190"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6440","DOI":"10.1002\/jcp.26539","article-title":"Targeting the phosphatidylinositol 3-kinase\/Akt\/mechanistic target of rapamycin signaling pathway in B-lineage acute lymphoblastic leukemia: An update","volume":"233","author":"Simioni","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1182\/blood-2009-02-206722","article-title":"High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia","volume":"114","author":"Gutierrez","year":"2009","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/nrc.2017.121","article-title":"Targeting B cell receptor signalling in cancer: Preclinical and clinical advances","volume":"18","author":"Burger","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"819","DOI":"10.3324\/haematol.2009.013797","article-title":"Role of the PI3K\/AKT and mTOR signaling pathways in acute myeloid leukemia","volume":"95","author":"Park","year":"2010","journal-title":"Haematologica"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/s10555-024-10203-9","article-title":"Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia","volume":"43","author":"Lill","year":"2024","journal-title":"Cancer Metastasis Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1182\/bloodadvances.2022007528","article-title":"Impact of mesenchymal stromal cell-derived vesicular cargo on B-cell acute lymphoblastic leukemia progression","volume":"7","author":"Karantanou","year":"2023","journal-title":"Blood Adv."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1182\/asheducation-2009.1.353","article-title":"The role of NOTCH1 signaling in T-ALL","volume":"2009","author":"Ferrando","year":"2009","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/science.1102160","article-title":"Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia","volume":"306","author":"Weng","year":"2004","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Kuek, V., Hughes, A.M., Kotecha, R.S., and Cheung, L.C. (2021). Therapeutic Targeting of the Leukaemia Microenvironment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136888"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Sottoriva, K., and Pajcini, K.V. (2021). Notch Signaling in the Bone Marrow Lymphopoietic Niche. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.723055"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6506","DOI":"10.1182\/blood-2011-08-376061","article-title":"Notch signaling in acute lymphoblastic leukemia: Any role for stromal microenvironment?","volume":"118","author":"Krampera","year":"2011","journal-title":"Blood"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"36523","DOI":"10.1074\/jbc.M006415200","article-title":"Cell cycle arrest and apoptosis induced by Notch1 in B cells","volume":"275","author":"Morimura","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/sj.cdd.4401253","article-title":"Notch1 enhances B-cell receptor-induced apoptosis in mature activated B cells without affecting cell cycle progression and surface IgM expression","volume":"10","author":"Romer","year":"2003","journal-title":"Cell Death Differ"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Patel, S.K., Zhdanovskaya, N., Sergio, I., Cardinale, A., Rosichini, M., Varricchio, C., Pace, E., Capalbo, C., Locatelli, F., and Macone, A. (2024). Thymic-Epithelial-Cell-Dependent Microenvironment Influences Proliferation and Apoptosis of Leukemic Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031412"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1038\/leu.2015.113","article-title":"The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia","volume":"29","author":"Eswaran","year":"2015","journal-title":"Leukemia"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/BS9.0000000000000026","article-title":"The regulators of BCR signaling during B cell activation","volume":"1","author":"Wen","year":"2019","journal-title":"Blood Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12943-018-0779-z","article-title":"Role of Bruton\u2019s tyrosine kinase in B cells and malignancies","volume":"17","author":"Dammeijer","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ccell.2015.02.003","article-title":"Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia","volume":"27","author":"Geng","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/leu.2016.9","article-title":"Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K\/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition","volume":"30","author":"Kohrer","year":"2016","journal-title":"Leukemia"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s43556-023-00126-2","article-title":"Epigenetic regulation and therapeutic targets in the tumor microenvironment","volume":"4","author":"Xie","year":"2023","journal-title":"Mol. Biomed."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Burke, M.J., and Bhatla, T. (2014). Epigenetic modifications in pediatric acute lymphoblastic leukemia. Front. Pediatr., 2.","DOI":"10.3389\/fped.2014.00042"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Mackowska, N., Drobna-Sledzinska, M., Witt, M., and Dawidowska, M. (2021). DNA Methylation in T-Cell Acute Lymphoblastic Leukemia: In Search for Clinical and Biological Meaning. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031388"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40364-017-0081-z","article-title":"DNA methyltransferases and their roles in tumorigenesis","volume":"5","author":"Zhang","year":"2017","journal-title":"Biomark. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41698-025-01003-7","article-title":"Epigenetic regulators in cancer therapy and progression","volume":"9","author":"Marei","year":"2025","journal-title":"NPJ Precis. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1038\/leu.2017.89","article-title":"Dnmt3a regulates T-cell development and suppresses T-ALL transformation","volume":"31","author":"Kramer","year":"2017","journal-title":"Leukemia"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"76898","DOI":"10.18632\/oncotarget.20176","article-title":"DNMT3B overexpression contributes to aberrant DNA methylation and MYC-driven tumor maintenance in T-ALL and Burkitt\u2019s lymphoma","volume":"8","author":"Poole","year":"2017","journal-title":"Oncotarget"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e2110758118","DOI":"10.1073\/pnas.2110758118","article-title":"TET2 as a tumor suppressor and therapeutic target in T-cell acute lymphoblastic leukemia","volume":"118","author":"Bensberg","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s13148-010-0016-0","article-title":"Molecular marks for epigenetic identification of developmental and cancer stem cells","volume":"2","author":"Patra","year":"2011","journal-title":"Clin. Epigenetics"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1097\/BS9.0000000000000071","article-title":"Abnormal bone marrow microenvironment: The \u201charbor\u201d of acute lymphoblastic leukemia cells","volume":"3","author":"Chen","year":"2021","journal-title":"Blood Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00018-020-03599-4","article-title":"Regulation of histone deacetylase activities and functions by phosphorylation and its physiological relevance","volume":"78","author":"Bahl","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/s41419-023-06019-0","article-title":"Histone acetylation by HBO1 (KAT7) activates Wnt\/beta-catenin signaling to promote leukemogenesis in B-cell acute lymphoblastic leukemia","volume":"14","author":"Wang","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Arif, K.M.T., Elliott, E.K., Haupt, L.M., and Griffiths, L.R. (2020). Regulatory Mechanisms of Epigenetic miRNA Relationships in Human Cancer and Potential as Therapeutic Targets. Cancers, 12.","DOI":"10.3390\/cancers12102922"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Catalanotto, C., Cogoni, C., and Zardo, G. (2016). MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101712"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, J., Hayder, H., Zayed, Y., and Peng, C. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00402"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Conti, I., Simioni, C., Varano, G., Brenna, C., Costanzi, E., and Neri, L.M. (2021). MicroRNAs Patterns as Potential Tools for Diagnostic and Prognostic Follow-Up in Cancer Survivorship. Cells, 10.","DOI":"10.3390\/cells10082069"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Conti, I., Varano, G., Simioni, C., Laface, I., Milani, D., Rimondi, E., and Neri, L.M. (2020). miRNAs as Influencers of Cell-Cell Communication in Tumor Microenvironment. Cells, 9.","DOI":"10.3390\/cells9010220"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5642","DOI":"10.1002\/jcp.26290","article-title":"Roles and clinical implications of microRNAs in acute lymphoblastic leukemia","volume":"233","author":"Ultimo","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Ortiz-Quintero, B. (2020). Extracellular MicroRNAs as Intercellular Mediators and Noninvasive Biomarkers of Cancer. Cancers, 12.","DOI":"10.3390\/cancers12113455"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1093\/jimmun\/vkaf203","article-title":"Regulation of B-cell development and differentiation by microRNAs during immune response and their implications in immunological disorders","volume":"214","author":"Roy","year":"2025","journal-title":"J. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1158\/1541-7786.MCR-15-0474","article-title":"Bone Marrow Microenvironment Niche Regulates miR-221\/222 in Acute Lymphoblastic Leukemia","volume":"14","author":"Moses","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.omtn.2022.02.005","article-title":"miR-221\/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review","volume":"27","author":"Arbitrio","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1158\/0008-5472.CAN-20-1145","article-title":"Evolution of the Epigenetic Landscape in Childhood B Acute Lymphoblastic Leukemia and Its Role in Drug Resistance","volume":"80","author":"Evensen","year":"2020","journal-title":"Cancer Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s44313-025-00107-0","article-title":"Unveiling the role of microRNAs, the PI3K\/AKT pathway, and their associations in various types of leukemia: A comprehensive review","volume":"60","author":"Chahardehi","year":"2025","journal-title":"Blood Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"155091","DOI":"10.1016\/j.prp.2024.155091","article-title":"MicroRNA-21\u2019s role in PTEN suppression and PI3K\/AKT activation: Implications for cancer biology","volume":"254","author":"Chawra","year":"2024","journal-title":"Pathol. Res. Pract."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1038\/bjc.2013.562","article-title":"MicroRNA-100\/99a, deregulated in acute lymphoblastic leukaemia, suppress proliferation and promote apoptosis by regulating the FKBP51 and IGF1R\/mTOR signalling pathways","volume":"109","author":"Li","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/ncb2037","article-title":"Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia","volume":"12","author":"Mavrakis","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1093\/nar\/gks175","article-title":"MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia","volume":"40","author":"Ye","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.mam.2012.06.005","article-title":"miRNAs and cancer: An epigenetics view","volume":"34","author":"Malumbres","year":"2013","journal-title":"Mol. Aspects Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.ccell.2016.03.013","article-title":"Genetic and Epigenetic Silencing of MicroRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression","volume":"29","author":"Bueno","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/onc.2011.248","article-title":"Methylation-mediated repression of microRNA-143 enhances MLL-AF4 oncogene expression","volume":"31","author":"Dou","year":"2012","journal-title":"Oncogene"},{"key":"ref_134","first-page":"2903","article-title":"The functional role of microRNA in acute lymphoblastic leukemia: Relevance for diagnosis, differential diagnosis, prognosis, and therapy","volume":"8","author":"Luan","year":"2015","journal-title":"Onco Targets Ther."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41392-024-02039-0","article-title":"Epigenetics-targeted drugs: Current paradigms and future challenges","volume":"9","author":"Dai","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"101821","DOI":"10.1016\/j.tranon.2023.101821","article-title":"Epigenetic modifications: Key players in cancer heterogeneity and drug resistance","volume":"39","author":"Sadida","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1038\/nm909","article-title":"Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia","volume":"9","author":"Matsunaga","year":"2003","journal-title":"Nat. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.leukres.2017.01.030","article-title":"Epigenetic drug combination overcomes osteoblast-induced chemoprotection in pediatric acute lymphoid leukemia","volume":"56","author":"Quagliano","year":"2017","journal-title":"Leuk. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1080\/15592294.2022.2118947","article-title":"Aberrant regulation of CXCR4 in cancer via deviant microRNA-targeted interactions","volume":"17","author":"Stuckel","year":"2022","journal-title":"Epigenetics"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41598-023-50628-w","article-title":"Plasma-derived exosomal miR-326, a prognostic biomarker and novel candidate for treatment of drug resistant pediatric acute lymphoblastic leukemia","volume":"14","author":"Saffari","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1007\/s00277-024-06181-1","article-title":"The molecular impact of miR-326 in acute lymphoblastic leukemia and its cross talk with P53","volume":"104","author":"Shafieizadegan","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"154789","DOI":"10.1016\/j.prp.2023.154789","article-title":"MicroRNA-155 and cancer metastasis: Regulation of invasion, migration, and epithelial-to-mesenchymal transition","volume":"250","author":"Moutabian","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Wang, S., Jin, S., Zhang, J., and Wang, X. (2025). Exosomal miRNAs: Key Regulators of the Tumor Microenvironment and Cancer Stem Cells. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199323"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"111263","DOI":"10.1016\/j.cellsig.2024.111263","article-title":"MicroRNAs in extracellular vesicles: A potential role in cancer progression","volume":"121","author":"Parashar","year":"2024","journal-title":"Cell Signal."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/10428194.2018.1459606","article-title":"Extracellular vesicles in hematological malignancies","volume":"60","author":"Litwinska","year":"2019","journal-title":"Leuk. Lymphoma"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"6383","DOI":"10.7150\/jca.98426","article-title":"Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion","volume":"15","author":"Mir","year":"2024","journal-title":"J. Cancer"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"100833","DOI":"10.1016\/j.drup.2022.100833","article-title":"The role of extracellular vesicles in the transfer of drug resistance competences to cancer cells","volume":"62","author":"Xavier","year":"2022","journal-title":"Drug Resist. Updat."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nrc1816","article-title":"Infection, immune responses and the aetiology of childhood leukaemia","volume":"6","author":"Greaves","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1182\/blood.2021011557","article-title":"The age of the bone marrow microenvironment influences B-cell acute lymphoblastic leukemia progression via CXCR5-CXCL13","volume":"138","author":"Zanetti","year":"2021","journal-title":"Blood"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature11885","article-title":"Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches","volume":"495","author":"Ding","year":"2013","journal-title":"Nature"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Mendiola-Soto, D.K., Barcenas-Lopez, D.A., Perez-Amado, C.J., Cruz-Miranda, G.M., Mejia-Arangure, J.M., Ramirez-Bello, J., Hidalgo-Miranda, A., and Jimenez-Morales, S. (2023). MiRNAs in Hematopoiesis and Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065436"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/5\/467\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T05:23:05Z","timestamp":1772860985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/5\/467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":151,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["cells15050467"],"URL":"https:\/\/doi.org\/10.3390\/cells15050467","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,5]]}}}