{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:20:07Z","timestamp":1793737207953,"version":"4.6.1"},"reference-count":149,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP240054"],"award-info":[{"award-number":["RP240054"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Mol Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Current intensified chemotherapy regimens have significantly increased survival rates for pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL), but these treatments can result in serious adverse effects; furthermore, patients who are resistant to chemotherapy or who relapse have inferior outcomes, together highlighting the need for improved therapeutic strategies. Despite recent advances in stratifying T-ALL into molecular subtypes with distinct driver mutations, efforts to target the tumor-intrinsic genomic alterations critical for T-ALL progression have yet to translate into more effective and less toxic therapies. Ample evidence now indicates that extrinsic factors in the leukemic microenvironment are critical for T-ALL growth, infiltration, and therapeutic resistance. Considering the diversity of organs infiltrated by T-ALL cells and the unique cellular components of the microenvironment encountered at each site, it is likely that there are both shared features of tumor-supportive niches across multiple organs and site-specific features that are key to leukemia cell survival. Therefore, elucidating the distinct microenvironmental cues supporting T-ALL in different anatomic locations could reveal novel therapeutic targets to improve therapies. This review summarizes the current understanding of the intricate interplay between leukemia cells and the diverse cells they encounter within their tumor microenvironments (TMEs), as well as opportunities to therapeutically target the leukemic microenvironment.<\/jats:p>","DOI":"10.1038\/s12276-024-01335-7","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T21:02:59Z","timestamp":1730408579000},"page":"2337-2347","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL)"],"prefix":"10.1038","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3044-4887","authenticated-orcid":false,"given":"Aram","family":"Lyu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo Hee","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan S.","family":"Humphrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terzah M.","family":"Horton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren I. R.","family":"Ehrlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"1335_CR1","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1056\/NEJMra1400972","volume":"373","author":"SP Hunger","year":"2015","unstructured":"Hunger, S. P. & Mullighan, C. G. Acute lymphoblastic leukemia in children. N. Engl. J. Med. 373, 1541\u20131552 (2015).","journal-title":"N. Engl. J. Med."},{"key":"1335_CR2","doi-asserted-by":"publisher","first-page":"e577","DOI":"10.1038\/bcj.2017.53","volume":"7","author":"T Terwilliger","year":"2017","unstructured":"Terwilliger, T. & Abdul-Hay, M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 7, e577\u2013e577 (2017).","journal-title":"Blood Cancer J."},{"key":"1335_CR3","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1080\/10408363.2019.1613629","volume":"56","author":"V Sas","year":"2019","unstructured":"Sas, V. et al. Transient leukemia of Down syndrome. Crit. Rev. Clin. Lab Sci. 56, 247\u2013259 (2019).","journal-title":"Crit. Rev. Clin. Lab Sci."},{"key":"1335_CR4","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1056\/NEJMra023001","volume":"350","author":"C-H Pui","year":"2004","unstructured":"Pui, C.-H., Relling, M. V. & Downing, J. R. Acute lymphoblastic leukemia. N. Engl. J. Med. 350, 1535\u20131548 (2004).","journal-title":"N. Engl. J. Med."},{"key":"1335_CR5","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.blre.2017.08.006","volume":"32","author":"E Vadillo","year":"2018","unstructured":"Vadillo, E., Dorantes-Acosta, E., Pelayo, R. & Schnoor, M. T cell acute lymphoblastic leukemia (T-ALL): new insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies. Blood Rev. 32, 36\u201351 (2018).","journal-title":"Blood Rev."},{"key":"1335_CR6","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/nrc.2016.63","volume":"16","author":"L Belver","year":"2016","unstructured":"Belver, L. & Ferrando, A. The genetics and mechanisms of T cell acute lymphoblastic leukaemia. Nat. Rev. Cancer 16, 494\u2013507 (2016).","journal-title":"Nat. Rev. Cancer"},{"key":"1335_CR7","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.3324\/haematol.2020.247031","volume":"105","author":"H Inaba","year":"2020","unstructured":"Inaba, H. & Mullighan, C. G. Pediatric acute lymphoblastic leukemia. Haematologica 105, 2524\u20132539 (2020).","journal-title":"Haematologica"},{"key":"1335_CR8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1182\/hematology.2022000337","volume":"2022","author":"KM O\u2019Dwyer","year":"2022","unstructured":"O\u2019Dwyer, K. M. Optimal approach to T-cell ALL. Hematology 2022, 197\u2013205 (2022).","journal-title":"Hematology"},{"key":"1335_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.710163","volume":"11","author":"ZN Al-Mahayri","year":"2021","unstructured":"Al-Mahayri, Z. N., AlAhmad, M. M. & Ali, B. R. Long-term effects of pediatric acute lymphoblastic leukemia chemotherapy: can recent findings inform old strategies? Front. Oncol. 11, 710163 (2021).","journal-title":"Front. Oncol."},{"key":"1335_CR10","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1200\/JCO.1997.15.6.2214","volume":"15","author":"FM Uckun","year":"1997","unstructured":"Uckun, F. M. et al. Clinical features and treatment outcome of childhood T-lineage acute lymphoblastic leukemia according to the apparent maturational stage of T-lineage leukemic blasts: a Children\u2019s Cancer Group study. J. Clin. Oncol. 15, 2214\u20132221 (1997).","journal-title":"J. Clin. Oncol."},{"key":"1335_CR11","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S1535-6108(02)00018-1","volume":"1","author":"AA Ferrando","year":"2002","unstructured":"Ferrando, A. A. et al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 1, 75\u201387 (2002).","journal-title":"Cancer Cell"},{"key":"1335_CR12","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1038\/s41588-022-01159-z","volume":"54","author":"SW Brady","year":"2022","unstructured":"Brady, S. W. et al. The genomic landscape of pediatric acute lymphoblastic leukemia. Nat. Genet. 54, 1376\u20131389 (2022).","journal-title":"Nat. Genet."},{"key":"1335_CR13","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1182\/blood.2023020678","volume":"142","author":"BL Wood","year":"2023","unstructured":"Wood, B. L. et al. Prognostic significance of ETP phenotype and minimal residual disease in T-ALL: a Children\u2019s Oncology Group study. Blood 142, 2069\u20132078 (2023).","journal-title":"Blood"},{"key":"1335_CR14","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S1470-2045(08)70314-0","volume":"10","author":"E Coustan-Smith","year":"2009","unstructured":"Coustan-Smith, E. et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 10, 147\u2013156 (2009).","journal-title":"Lancet Oncol."},{"key":"1335_CR15","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1182\/blood-2015-08-661702","volume":"127","author":"N Jain","year":"2016","unstructured":"Jain, N. et al. Early T-cell precursor acute lymphoblastic leukemia\/lymphoma (ETP-ALL\/LBL) in adolescents and adults: a high-risk subtype. Blood 127, 1863\u20131869 (2016).","journal-title":"Blood"},{"key":"1335_CR16","doi-asserted-by":"publisher","first-page":"e80","DOI":"10.1016\/S2352-3026(15)00254-9","volume":"3","author":"V Conter","year":"2016","unstructured":"Conter, V. et al. Early T-cell precursor acute lymphoblastic leukaemia in children treated in AIEOP centres with AIEOP-BFM protocols: a retrospective analysis. Lancet Haematol. 3, e80\u2013e86 (2016).","journal-title":"Lancet Haematol."},{"key":"1335_CR17","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.750789","volume":"11","author":"C Sin","year":"2021","unstructured":"Sin, C. & Man, P. M. Early T-Cell precursor acute lymphoblastic leukemia: diagnosis, updates in molecular pathogenesis, management, and novel therapies. Front. Oncol. 11, 750789 (2021).","journal-title":"Front. Oncol."},{"key":"1335_CR18","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1038\/ng.3909","volume":"49","author":"Y Liu","year":"2017","unstructured":"Liu, Y. et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat. Genet. 49, 1211\u20131218 (2017).","journal-title":"Nat. Genet."},{"key":"1335_CR19","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/nature10725","volume":"481","author":"J Zhang","year":"2012","unstructured":"Zhang, J. et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 481, 157\u2013163 (2012).","journal-title":"Nature"},{"key":"1335_CR20","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1084\/jem.20122727","volume":"211","author":"LM Treanor","year":"2014","unstructured":"Treanor, L. M. et al. Interleukin-7 receptor mutants initiate early T cell precursor leukemia in murine thymocyte progenitors with multipotent potential. J. Exp. Med. 211, 701\u2013713 (2014).","journal-title":"J. Exp. Med."},{"key":"1335_CR21","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1038\/sj.leu.2401382","volume":"13","author":"T Niehues","year":"1999","unstructured":"Niehues, T. et al. A classification based on T cell selection-related phenotypes identifies a subgroup of childhood T-ALL with favorable outcome in the COALL studies. Leukemia 13, 614\u2013617 (1999).","journal-title":"Leukemia"},{"key":"1335_CR22","doi-asserted-by":"publisher","first-page":"316","DOI":"10.3389\/fonc.2019.00316","volume":"9","author":"EP Noronha","year":"2019","unstructured":"Noronha, E. P. et al. The profile of immunophenotype and genotype aberrations in subsets of pediatric T-Cell acute lymphoblastic leukemia. Front. Oncol. 9, 316 (2019).","journal-title":"Front. Oncol."},{"key":"1335_CR23","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.ccr.2011.02.008","volume":"19","author":"I Homminga","year":"2011","unstructured":"Homminga, I. et al. Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T Cell acute lymphoblastic leukemia. Cancer Cell 19, 484\u2013497 (2011).","journal-title":"Cancer Cell"},{"key":"1335_CR24","doi-asserted-by":"publisher","first-page":"273","DOI":"10.3389\/fonc.2020.00273","volume":"10","author":"B Fattizzo","year":"2020","unstructured":"Fattizzo, B., Rosa, J., Giannotta, J. A., Baldini, L. & Fracchiolla, N. S. The physiopathology of T- Cell acute lymphoblastic leukemia: focus on molecular aspects. Front. Oncol. 10, 273 (2020).","journal-title":"Front. Oncol."},{"key":"1335_CR25","first-page":"933","volume":"7","author":"A Kikuchi","year":"1993","unstructured":"Kikuchi, A. et al. Clinical significance of TAL1 gene alteration in childhood T-cell acute lymphoblastic leukemia and lymphoma. Leukemia 7, 933\u2013938 (1993).","journal-title":"Leukemia"},{"key":"1335_CR26","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1182\/blood.V81.8.2110.2110","volume":"81","author":"RO Bash","year":"1993","unstructured":"Bash, R. O. et al. Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study. Blood 81, 2110\u20132117 (1993).","journal-title":"Blood"},{"key":"1335_CR27","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1182\/blood-2016-10-706465","volume":"129","author":"T Girardi","year":"2017","unstructured":"Girardi, T., Vicente, C., Cools, J. & Keersmaecker, K. D. The genetics and molecular biology of T-ALL. Blood 129, 1113\u20131123 (2017).","journal-title":"Blood"},{"key":"1335_CR28","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1182\/asheducation-2016.1.580","volume":"2016","author":"EA Raetz","year":"2016","unstructured":"Raetz, E. A. & Teachey, D. T. T-cell acute lymphoblastic leukemia. Hematology 2016, 580\u2013588 (2016).","journal-title":"Hematology"},{"key":"1335_CR29","first-page":"3019","volume":"141","author":"SJS Lim","year":"2023","unstructured":"Lim, S. J. S., Ford, J. B. & Hermiston, M. L. How I treat newly diagnosed and refractory T-cell acute lymphoblastic lymphoma in children and young adults. Blood 141, 3019\u20133030 (2023).","journal-title":"Blood"},{"key":"1335_CR30","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1182\/bloodadvances.2023010303","volume":"8","author":"S Shimony","year":"2024","unstructured":"Shimony, S., DeAngelo, D. J. & Luskin, M. R. Nelarabine: when and how to use in the treatment of T-cell acute lymphoblastic leukemia. Blood Adv. 8, 23\u201336 (2024).","journal-title":"Blood Adv."},{"key":"1335_CR31","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1200\/JCO.21.02678","volume":"40","author":"DT Teachey","year":"2022","unstructured":"Teachey, D. T. et al. Children\u2019s oncology group Trial AALL1231: a Phase III clinical trial testing Bortezomib in newly diagnosed T-Cell acute lymphoblastic leukemia and lymphoma. J. Clin. Oncol. 40, 2106\u20132118 (2022).","journal-title":"J. Clin. Oncol."},{"key":"1335_CR32","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1111\/bjh.14875","volume":"179","author":"A Malone","year":"2017","unstructured":"Malone, A. & Smith, O. P. Nelarabine toxicity in children and adolescents with relapsed\/refractory T\u2010ALL\/T\u2010LBL: can we avoid throwing the baby out with the bathwater? Br. J. Haematol. 179, 179\u2013181 (2017).","journal-title":"Br. J. Haematol."},{"key":"1335_CR33","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/nm.3078","volume":"19","author":"G Tzoneva","year":"2013","unstructured":"Tzoneva, G. et al. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nat. Med. 19, 368\u2013371 (2013).","journal-title":"Nat. Med."},{"key":"1335_CR34","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1182\/blood-2019-01-852392","volume":"133","author":"CL Dieck","year":"2019","unstructured":"Dieck, C. L. & Ferrando, A. Genetics and mechanisms of NT5C2-driven chemotherapy resistance in relapsed ALL. Blood 133, 2263\u20132268 (2019).","journal-title":"Blood"},{"key":"1335_CR35","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1084\/jem.20110105","volume":"208","author":"E Clappier","year":"2011","unstructured":"Clappier, E. et al. Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse. J. Exp. Med. 208, 653\u2013661 (2011).","journal-title":"J. Exp. Med."},{"key":"1335_CR36","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1158\/2643-3230.BCD-20-0093","volume":"2","author":"V Cordo\u2019","year":"2021","unstructured":"Cordo\u2019, V., van der Zwet, J. C. G., Cant\u00e9-Barrett, K., Pieters, R. & Meijerink, J. P. P. T-cell acute lymphoblastic leukemia: a roadmap to targeted therapies. Blood Cancer Discov. 2, 19\u201331 (2021).","journal-title":"Blood Cancer Discov."},{"key":"1335_CR37","doi-asserted-by":"publisher","first-page":"6585","DOI":"10.1200\/jco.2006.24.18_suppl.6585","volume":"24","author":"DJ Deangelo","year":"2006","unstructured":"Deangelo, D. J. et al. A phase I clinical trial of the notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia\/lymphoma (T-ALL) and other leukemias. J. Clin. Oncol. 24, 6585 (2006).","journal-title":"J. Clin. Oncol."},{"key":"1335_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.80","volume":"5","author":"C Papayannidis","year":"2015","unstructured":"Papayannidis, C. et al. 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. Blood Cancer J. 5, e350 (2015).","journal-title":"Blood Cancer J."},{"key":"1335_CR39","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/ajh.24568","volume":"92","author":"BK Ragon","year":"2017","unstructured":"Ragon, B. K. et al. Buparlisib, a PI3K inhibitor, demonstrates acceptable tolerability and preliminary activity in a phase I trial of patients with advanced leukemias. Am. J. Hematol. 92, 7\u201311 (2017).","journal-title":"Am. J. Hematol."},{"key":"1335_CR40","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1182\/blood-2008-02-138172","volume":"113","author":"F Armstrong","year":"2009","unstructured":"Armstrong, F. et al. NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity. Blood 113, 1730\u20131740 (2009).","journal-title":"Blood"},{"key":"1335_CR41","doi-asserted-by":"publisher","first-page":"E1016","DOI":"10.1073\/pnas.1520245113","volume":"113","author":"TA Triplett","year":"2016","unstructured":"Triplett, T. A. et al. Endogenous dendritic cells from the tumor microenvironment support T-ALL growth via IGF1R activation. Proc. Natl Acad. Sci. USA 113, E1016\u2013E1025 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1335_CR42","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1182\/blood.2020007145","volume":"136","author":"A Lyu","year":"2020","unstructured":"Lyu, A. et al. Tumor-associated myeloid cells provide critical support for T-ALL. Blood 136, 1837\u20131850 (2020).","journal-title":"Blood"},{"key":"1335_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41925-z","volume":"14","author":"A Lyu","year":"2023","unstructured":"Lyu, A. et al. Integrin signaling is critical for myeloid-mediated support of T-cell acute lymphoblastic leukemia. Nat. Commun. 14, 6270 (2023).","journal-title":"Nat. Commun."},{"key":"1335_CR44","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.it.2017.10.007","volume":"39","author":"JN Lancaster","year":"2018","unstructured":"Lancaster, J. N., Li, Y. & Ehrlich, L. I. R. Chemokine-mediated choreography of thymocyte development and selection. Trends Immunol. 39, 86\u201398 (2018).","journal-title":"Trends Immunol."},{"key":"1335_CR45","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/s41577-023-00911-8","volume":"24","author":"KM Ashby","year":"2024","unstructured":"Ashby, K. M. & Hogquist, K. A. A guide to thymic selection of T cells. Nat. Rev. Immunol. 24, 103\u2013117 (2024).","journal-title":"Nat. Rev. Immunol."},{"key":"1335_CR46","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.1084\/jem.20080829","volume":"205","author":"U Koch","year":"2008","unstructured":"Koch, U. et al. Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment. J. Exp. Med. 205, 2515\u20132523 (2008).","journal-title":"J. Exp. Med."},{"key":"1335_CR47","doi-asserted-by":"publisher","first-page":"6173","DOI":"10.4049\/jimmunol.1202573","volume":"190","author":"S Shitara","year":"2013","unstructured":"Shitara, S. et al. IL-7 produced by thymic epithelial cells plays a major role in the development of thymocytes and TCR\u03b3\u03b4+ intraepithelial lymphocytes. J. Immunol. 190, 6173\u20136179 (2013).","journal-title":"J. Immunol."},{"key":"1335_CR48","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1084\/jem.180.5.1955","volume":"180","author":"JJ Peschon","year":"1994","unstructured":"Peschon, J. J. et al. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J. Exp. Med. 180, 1955\u20131960 (1994).","journal-title":"J. Exp. Med."},{"key":"1335_CR49","doi-asserted-by":"publisher","first-page":"60","DOI":"10.4049\/jimmunol.174.1.60","volume":"174","author":"M Zamisch","year":"2005","unstructured":"Zamisch, M. et al. Ontogeny and regulation of IL-7-Expressing thymic epithelial cells. J. Immunol. 174, 60\u201367 (2005).","journal-title":"J. Immunol."},{"key":"1335_CR50","doi-asserted-by":"publisher","first-page":"e7637","DOI":"10.1371\/journal.pone.0007637","volume":"4","author":"RI Mazzucchelli","year":"2009","unstructured":"Mazzucchelli, R. I. et al. Visualization and identification of IL-7 producing cells in reporter mice. PLoS ONE 4, e7637 (2009).","journal-title":"PLoS ONE"},{"key":"1335_CR51","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/nri2023","volume":"7","author":"R Mazzucchelli","year":"2007","unstructured":"Mazzucchelli, R. & Durum, S. K. Interleukin-7 receptor expression: intelligent design. Nat. Rev. Immunol. 7, 144\u2013154 (2007).","journal-title":"Nat. Rev. Immunol."},{"key":"1335_CR52","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S1074-7613(00)80517-8","volume":"7","author":"U Freeden-Jeffry","year":"1997","unstructured":"Freeden-Jeffry, U., von, Solvason, N., Howard, M. & Murray, R. The Earliest T Lineage\u2013committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. Immunity 7, 147\u2013154 (1997).","journal-title":"Immunity"},{"key":"1335_CR53","doi-asserted-by":"publisher","first-page":"4017","DOI":"10.4049\/jimmunol.1302259","volume":"192","author":"DK Shah","year":"2014","unstructured":"Shah, D. K. & Z\u00fa\u00f1iga-Pfl\u00fccker, J. C. An overview of the intrathymic intricacies of T Cell development. J. Immunol. 192, 4017\u20134023 (2014).","journal-title":"J. Immunol."},{"key":"1335_CR54","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1002\/eji.200323831","volume":"33","author":"C Trigueros","year":"2003","unstructured":"Trigueros, C. et al. Pre\u2010TCR signaling regulates IL\u20107 receptor \u03b1 expression promoting thymocyte survival at the transition from the double\u2010negative to double\u2010positive stage. Eur. J. Immunol. 33, 1968\u20131977 (2003).","journal-title":"Eur. J. Immunol."},{"key":"1335_CR55","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.smim.2012.02.002","volume":"24","author":"C Hong","year":"2012","unstructured":"Hong, C., Luckey, M. A. & Park, J.-H. Intrathymic IL-7: the where, when, and why of IL-7 signaling during T cell development. Semin. Immunol. 24, 151\u2013158 (2012).","journal-title":"Semin. Immunol."},{"key":"1335_CR56","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/ni.3122","volume":"16","author":"A Boudil","year":"2015","unstructured":"Boudil, A. et al. IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte \u03b2-selection. Nat. Immunol. 16, 397\u2013405 (2015).","journal-title":"Nat. Immunol."},{"key":"1335_CR57","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1182\/blood.2019000553","volume":"138","author":"A Silva","year":"2021","unstructured":"Silva, A. et al. Overexpression of wild-type IL-7R\u03b1 promotes T-cell acute lymphoblastic leukemia\/lymphoma. Blood 138, 1040\u20131052 (2021).","journal-title":"Blood"},{"key":"1335_CR58","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1182\/blood-2023-186699","volume":"142","author":"L Courtois","year":"2023","unstructured":"Courtois, L. et al. IL7-receptor expression is frequent in T-cell acute lymphoblastic leukemia and predicts sensitivity to JAK-inhibition. Blood 142, 158\u2013171 (2023).","journal-title":"Blood"},{"key":"1335_CR59","first-page":"1229","volume":"88","author":"MT Scupoli","year":"2003","unstructured":"Scupoli, M. T. et al. Thymic epithelial cells promote survival of human T-cell acute lymphoblastic leukemia blasts: the role of interleukin-7. Haematologica 88, 1229\u20131237 (2003).","journal-title":"Haematologica"},{"key":"1335_CR60","doi-asserted-by":"publisher","first-page":"264","DOI":"10.3324\/haematol.10356","volume":"92","author":"MT Scupoli","year":"2007","unstructured":"Scupoli, M. T. et al. Interleukin 7 requirement for survival of T-cell acute lymphoblastic leukemia and human thymocytes on bone marrow stroma. Haematologica 92, 264\u2013266 (2007).","journal-title":"Haematologica"},{"key":"1335_CR61","doi-asserted-by":"publisher","first-page":"4780","DOI":"10.1158\/0008-5472.CAN-10-3606","volume":"71","author":"A Silva","year":"2011","unstructured":"Silva, A. et al. IL-7 contributes to the progression of human T-cell acute lymphoblastic leukemias. Cancer Res. 71, 4780\u20134789 (2011).","journal-title":"Cancer Res."},{"key":"1335_CR62","doi-asserted-by":"publisher","DOI":"10.5402\/2011\/921706","volume":"2011","author":"X Li","year":"2011","unstructured":"Li, X. & von Boehmer, H. Notch Signaling in T-Cell Development and T-ALL. ISRN Hematol. 2011, 921706 (2011).","journal-title":"ISRN Hematol."},{"key":"1335_CR63","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/S1074-7613(00)80054-0","volume":"10","author":"F Radtke","year":"1999","unstructured":"Radtke, F. et al. Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 10, 547\u2013558 (1999).","journal-title":"Immunity"},{"key":"1335_CR64","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S1074-7613(00)80105-3","volume":"11","author":"JC Pui","year":"1999","unstructured":"Pui, J. C. et al. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 11, 299\u2013308 (1999).","journal-title":"Immunity"},{"key":"1335_CR65","doi-asserted-by":"publisher","first-page":"2511","DOI":"10.1182\/blood-2011-04-346726","volume":"118","author":"J Shi","year":"2011","unstructured":"Shi, J., Fallahi, M., Luo, J.-L. & Petrie, H. T. Nonoverlapping functions for Notch1 and Notch3 during murine steady-state thymic lymphopoiesis. Blood 118, 2511\u20132519 (2011).","journal-title":"Blood"},{"key":"1335_CR66","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1073\/pnas.98.1.229","volume":"98","author":"G Struhl","year":"2001","unstructured":"Struhl, G. & Greenwald, I. Presenilin-mediated transmembrane cleavage is required for Notch signal transduction in Drosophila. Proc. Natl Acad. Sci. USA 98, 229\u2013234 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1335_CR67","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1101\/gad.1450406","volume":"20","author":"AP Weng","year":"2006","unstructured":"Weng, A. P. et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia\/lymphoma. Genes Dev. 20, 2096\u20132109 (2006).","journal-title":"Genes Dev."},{"key":"1335_CR68","doi-asserted-by":"publisher","first-page":"18261","DOI":"10.1073\/pnas.0606108103","volume":"103","author":"T Palomero","year":"2006","unstructured":"Palomero, T. et al. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc. Natl Acad. Sci. USA 103, 18261\u201318266 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1335_CR69","doi-asserted-by":"publisher","first-page":"8022","DOI":"10.1128\/MCB.01091-06","volume":"26","author":"VM Sharma","year":"2006","unstructured":"Sharma, V. M. et al. Notch1 contributes to mouse T-Cell leukemia by directly inducing the expression of c-myc. Mol. Cell Biol. 26, 8022\u20138031 (2006).","journal-title":"Mol. Cell Biol."},{"key":"1335_CR70","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1084\/jem.20110121","volume":"208","author":"H Medyouf","year":"2011","unstructured":"Medyouf, H. et al. High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signaling. J. Exp. Med. 208, 1809\u20131822 (2011).","journal-title":"J. Exp. Med."},{"key":"1335_CR71","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/0092-8674(91)90111-B","volume":"66","author":"LW Ellisen","year":"1991","unstructured":"Ellisen, L. W. et al. TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66, 649\u2013661 (1991).","journal-title":"Cell"},{"key":"1335_CR72","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1126\/science.1102160","volume":"306","author":"AP Weng","year":"2004","unstructured":"Weng, A. P. et al. Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia. Science 306, 269\u2013271 (2004).","journal-title":"Science"},{"key":"1335_CR73","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1084\/jem.20070872","volume":"204","author":"BJ Thompson","year":"2007","unstructured":"Thompson, B. J. et al. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J. Exp. Med. 204, 1825\u20131835 (2007).","journal-title":"J. Exp. Med."},{"key":"1335_CR74","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1084\/jem.20111855","volume":"208","author":"C Lobry","year":"2011","unstructured":"Lobry, C., Oh, P. & Aifantis, I. Oncogenic and tumor suppressor functions of Notch in cancer: it\u2019s NOTCH what you think. J. Exp. Med. 208, 1931\u20131935 (2011).","journal-title":"J. Exp. Med."},{"key":"1335_CR75","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1002\/j.1460-2075.1986.tb04528.x","volume":"5","author":"A Ullrich","year":"1986","unstructured":"Ullrich, A. et al. Insulin\u2010like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 5, 2503\u20132512 (1986).","journal-title":"EMBO J."},{"key":"1335_CR76","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1210\/endo.141.3.7360","volume":"141","author":"O Kecha","year":"2000","unstructured":"Kecha, O. et al. Involvement of insulin-like growth factors in early T cell development: a study using fetal thymic organ cultures 1. Endocrinology 141, 1209\u20131217 (2000).","journal-title":"Endocrinology"},{"key":"1335_CR77","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1007\/PL00000744","volume":"57","author":"TE Adams","year":"2000","unstructured":"Adams, T. E., Epa, V. C., Garrett, T. P. J. & Ward, C. W. Structure and function of the type 1 insulin-like growth factor receptor. Cell Mol. Life Sci. 57, 1050\u20131093 (2000).","journal-title":"Cell Mol. Life Sci."},{"key":"1335_CR78","doi-asserted-by":"publisher","first-page":"7088","DOI":"10.1073\/pnas.96.12.7088","volume":"96","author":"K Sj\u00f6gren","year":"1999","unstructured":"Sj\u00f6gren, K. et al. Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc. Natl Acad. Sci. USA 96, 7088\u20137092 (1999).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1335_CR79","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1136\/mp.54.5.311","volume":"54","author":"Z Laron","year":"2001","unstructured":"Laron, Z. Insulin-like growth factor 1 (IGF-1): a growth hormone. Mol. Pathol. 54, 311\u2013316 (2001).","journal-title":"Mol. Pathol."},{"key":"1335_CR80","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nrc1387","volume":"4","author":"MN Pollak","year":"2004","unstructured":"Pollak, M. N., Schernhammer, E. S. & Hankinson, S. E. Insulin-like growth factors and neoplasia. Nat. Rev. Cancer 4, 505\u2013518 (2004).","journal-title":"Nat. Rev. Cancer"},{"key":"1335_CR81","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2019.100652","volume":"74","author":"S Gusscott","year":"2019","unstructured":"Gusscott, S., Tamiro, F., Giambra, V. & Weng, A. P. Insulin-like growth factor (IGF) signaling in T-cell acute lymphoblastic leukemia. Adv. Biol. Regul. 74, 100652 (2019).","journal-title":"Adv. Biol. Regul."},{"key":"1335_CR82","doi-asserted-by":"publisher","first-page":"e0161158","DOI":"10.1371\/journal.pone.0161158","volume":"11","author":"S Gusscott","year":"2016","unstructured":"Gusscott, S. et al. IGF1R Derived PI3K\/AKT Signaling Maintains Growth in a Subset of Human T-Cell Acute Lymphoblastic Leukemias. PLoS ONE 11, e0161158 (2016).","journal-title":"PLoS ONE"},{"key":"1335_CR83","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.4049\/jimmunol.1400451","volume":"194","author":"S-Y Chen","year":"2015","unstructured":"Chen, S.-Y. et al. Organ-specific microenvironment modifies diverse functional and phenotypic characteristics of leukemia-associated macrophages in mouse T cell acute lymphoblastic leukemia. J. Immunol. 194, 2919\u20132929 (2015).","journal-title":"J. Immunol."},{"key":"1335_CR84","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.imbio.2017.10.009","volume":"223","author":"X Yang","year":"2018","unstructured":"Yang, X. et al. Hepatic leukemia-associated macrophages exhibit a pro-inflammatory phenotype in Notch1-induced acute T cell leukemia. Immunobiology 223, 73\u201380 (2018).","journal-title":"Immunobiology"},{"key":"1335_CR85","doi-asserted-by":"publisher","first-page":"3677","DOI":"10.1158\/0008-5472.CAN-20-0034","volume":"80","author":"F Yang","year":"2020","unstructured":"Yang, F. et al. Monocyte-derived leukemia-associated macrophages facilitate extramedullary distribution of T-cell acute lymphoblastic leukemia cells. Cancer Res. 80, 3677\u20133691 (2020).","journal-title":"Cancer Res."},{"key":"1335_CR86","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/nrrheum.2015.160","volume":"12","author":"MR Reagan","year":"2016","unstructured":"Reagan, M. R. & Rosen, C. J. Navigating the bone marrow niche: translational insights and cancer-driven dysfunction. Nat. Rev. Rheumatol. 12, 154\u2013168 (2016).","journal-title":"Nat. Rev. Rheumatol."},{"key":"1335_CR87","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/imr.12402","volume":"271","author":"D Passaro","year":"2016","unstructured":"Passaro, D., Quang, C. T. & Ghysdael, J. Microenvironmental cues for T\u2010cell acute lymphoblastic leukemia development. Immunol. Rev. 271, 156\u2013172 (2016).","journal-title":"Immunol. Rev."},{"key":"1335_CR88","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190589","volume":"217","author":"MT Witkowski","year":"2019","unstructured":"Witkowski, M. T., Kousteni, S. & Aifantis, I. Mapping and targeting of the leukemic microenvironment. J. Exp. Med. 217, e20190589 (2019).","journal-title":"J. Exp. Med."},{"key":"1335_CR89","doi-asserted-by":"publisher","first-page":"4821","DOI":"10.1182\/blood-2012-12-475483","volume":"121","author":"B Boyerinas","year":"2013","unstructured":"Boyerinas, B. et al. Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Blood 121, 4821\u20134831 (2013).","journal-title":"Blood"},{"key":"1335_CR90","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.ccell.2015.05.003","volume":"27","author":"D Passaro","year":"2015","unstructured":"Passaro, D. et al. CXCR4 is required for leukemia-initiating cell activity in T cell acute lymphoblastic leukemia. Cancer Cell 27, 769\u2013779 (2015).","journal-title":"Cancer Cell"},{"key":"1335_CR91","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.ccell.2015.05.002","volume":"27","author":"LA Pitt","year":"2015","unstructured":"Pitt, L. A. et al. CXCL12-producing vascular endothelial niches control acute T cell leukemia maintenance. Cancer Cell 27, 755\u2013768 (2015).","journal-title":"Cancer Cell"},{"key":"1335_CR92","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/nature12984","volume":"505","author":"SJ Morrison","year":"2014","unstructured":"Morrison, S. J. & Scadden, D. T. The bone marrow niche for haematopoietic stem cells. Nature 505, 327\u2013334 (2014).","journal-title":"Nature"},{"key":"1335_CR93","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nature11926","volume":"495","author":"A Greenbaum","year":"2013","unstructured":"Greenbaum, A. et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 495, 227\u2013230 (2013).","journal-title":"Nature"},{"key":"1335_CR94","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nature11885","volume":"495","author":"L Ding","year":"2013","unstructured":"Ding, L. & Morrison, S. J. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature 495, 231\u2013235 (2013).","journal-title":"Nature"},{"key":"1335_CR95","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1038\/nm1588","volume":"13","author":"Medyouf","year":"2007","unstructured":"Medyouf et al. Targeting calcineurin activation as a therapeutic strategy for T-cell acute lymphoblastic leukemia. Nat. Med. 13, 736\u2013741 (2007).","journal-title":"Nat. Med."},{"key":"1335_CR96","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.1038\/leu.2013.156","volume":"27","author":"S Gachet","year":"2013","unstructured":"Gachet, S. et al. Leukemia-initiating cell activity requires calcineurin in T-cell acute lymphoblastic leukemia. Leukemia 27, 2289\u20132300 (2013).","journal-title":"Leukemia"},{"key":"1335_CR97","doi-asserted-by":"publisher","first-page":"9398","DOI":"10.1073\/pnas.152665399","volume":"99","author":"OF Bueno","year":"2002","unstructured":"Bueno, O. F., Brandt, E. B., Rothenberg, M. E. & Molkentin, J. D. Defective T cell development and function in calcineurin A\u03b2-deficient mice. Proc. Natl Acad. Sci. USA 99, 9398\u20139403 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1335_CR98","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/S1074-7613(04)00052-4","volume":"20","author":"JR Neilson","year":"2004","unstructured":"Neilson, J. R., Winslow, M. M., Hur, E. M. & Crabtree, G. R. Calcineurin B1 is essential for positive but not negative selection during thymocyte development. Immunity 20, 255\u2013266 (2004).","journal-title":"Immunity"},{"key":"1335_CR99","doi-asserted-by":"publisher","first-page":"e205","DOI":"10.1016\/S1470-2045(12)70580-6","volume":"14","author":"D Bhojwani","year":"2013","unstructured":"Bhojwani, D. & Pui, C.-H. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 14, e205\u2013e217 (2013).","journal-title":"Lancet Oncol."},{"key":"1335_CR100","doi-asserted-by":"publisher","first-page":"5473","DOI":"10.1182\/blood-2006-05-021071","volume":"109","author":"C Gregorj","year":"2007","unstructured":"Gregorj, C. et al. ERK1\/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia. Blood 109, 5473\u20135476 (2007).","journal-title":"Blood"},{"key":"1335_CR101","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1002\/emmm.201303286","volume":"6","author":"B Uzan","year":"2014","unstructured":"Uzan, B. et al. Interleukin\u201018 produced by bone marrow\u2010derived stromal cells supports T\u2010cell acute leukaemia progression. EMBO Mol. Med. 6, 821\u2013834 (2014).","journal-title":"EMBO Mol. Med."},{"key":"1335_CR102","doi-asserted-by":"publisher","first-page":"763","DOI":"10.3389\/fimmu.2018.00763","volume":"9","author":"K Nakanishi","year":"2018","unstructured":"Nakanishi, K. Unique action of Interleukin-18 on T cells and other immune cells. Front. Immunol. 9, 763 (2018).","journal-title":"Front. Immunol."},{"key":"1335_CR103","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1182\/blood-2017-12-784132","volume":"131","author":"D Duarte","year":"2018","unstructured":"Duarte, D., Hawkins, E. D. & Celso, C. L. The interplay of leukemia cells and the bone marrow microenvironment. Blood 131, 1507\u20131511 (2018).","journal-title":"Blood"},{"key":"1335_CR104","doi-asserted-by":"publisher","first-page":"3901","DOI":"10.1242\/jcs.03098","volume":"119","author":"JD Humphries","year":"2006","unstructured":"Humphries, J. D., Byron, A. & Humphries, M. J. Integrin ligands at a glance. J. Cell Sci. 119, 3901\u20133903 (2006).","journal-title":"J. Cell Sci."},{"key":"1335_CR105","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1016\/j.bbagen.2014.01.010","volume":"1840","author":"F Gattazzo","year":"2014","unstructured":"Gattazzo, F., Urciuolo, A. & Bonaldo, P. Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim. Biophys. Acta 1840, 2506\u20132519 (2014).","journal-title":"Biochim. Biophys. Acta"},{"key":"1335_CR106","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s12026-014-8527-y","volume":"59","author":"NM Chapman","year":"2014","unstructured":"Chapman, N. M. & Houtman, J. C. D. Functions of the FAK family kinases in T cells: beyond actin cytoskeletal rearrangement. Immunol. Res. 59, 23\u201334 (2014).","journal-title":"Immunol. Res."},{"key":"1335_CR107","doi-asserted-by":"publisher","first-page":"106","DOI":"10.3389\/fendo.2015.00106","volume":"6","author":"OT Cox","year":"2015","unstructured":"Cox, O. T. et al. IGF-1 receptor and adhesion signaling: an important axis in determining cancer cell phenotype and therapy resistance. Front. Endocrinol. 6, 106 (2015).","journal-title":"Front. Endocrinol."},{"key":"1335_CR108","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.ccell.2019.01.007","volume":"35","author":"J Cooper","year":"2019","unstructured":"Cooper, J. & Giancotti, F. G. Integrin signaling in cancer: mechanotransduction, stemness, epithelial plasticity, and therapeutic resistance. Cancer Cell 35, 347\u2013367 (2019).","journal-title":"Cancer Cell"},{"key":"1335_CR109","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1046\/j.1365-2141.2001.03182.x","volume":"115","author":"SS Winter","year":"2001","unstructured":"Winter, S. S. et al. Enhanced T\u2010lineage acute lymphoblastic leukaemia cell survival on bone marrow stroma requires involvement of LFA\u20101 and ICAM\u20101. Br. J. Haematol. 115, 862\u2013871 (2001).","journal-title":"Br. J. Haematol."},{"key":"1335_CR110","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1593-2","volume":"10","author":"S Berrazouane","year":"2019","unstructured":"Berrazouane, S. et al. Beta1 integrin blockade overcomes doxorubicin resistance in human T-cell acute lymphoblastic leukemia. Cell Death Dis. 10, 357 (2019).","journal-title":"Cell Death Dis."},{"key":"1335_CR111","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/nature19801","volume":"538","author":"ED Hawkins","year":"2016","unstructured":"Hawkins, E. D. et al. T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments. Nature 538, 518\u2013522 (2016).","journal-title":"Nature"},{"key":"1335_CR112","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1084\/jem.20011475","volume":"195","author":"C Lancrin","year":"2002","unstructured":"Lancrin, C. et al. Major T cell progenitor activity in bone marrow\u2013derived spleen colonies. J. Exp. Med. 195, 919\u2013929 (2002).","journal-title":"J. Exp. Med."},{"key":"1335_CR113","doi-asserted-by":"publisher","first-page":"3511","DOI":"10.1182\/blood-2005-08-3454","volume":"107","author":"I Maillard","year":"2006","unstructured":"Maillard, I. et al. Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation. Blood 107, 3511\u20133519 (2006).","journal-title":"Blood"},{"key":"1335_CR114","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.7150\/thno.48067","volume":"11","author":"H Xiong","year":"2021","unstructured":"Xiong, H. et al. Spleen plays a major role in DLL4-driven acute T-cell lymphoblastic leukemia. Theranostics 11, 1594\u20131608 (2021).","journal-title":"Theranostics"},{"key":"1335_CR115","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1182\/bloodadvances.2021004177","volume":"5","author":"AD Grande","year":"2021","unstructured":"Grande, A. D. et al. The spleen as a sanctuary site for residual leukemic cells following ABT-199 monotherapy in ETP-ALL. Blood Adv. 5, 1963\u20131976 (2021).","journal-title":"Blood Adv."},{"key":"1335_CR116","doi-asserted-by":"publisher","DOI":"10.1038\/srep41427","volume":"7","author":"N Pelusi","year":"2017","unstructured":"Pelusi, N. et al. The spleen microenvironment influences disease transformation in a mouse model of KITD816V-dependent myeloproliferative neoplasm. Sci. Rep. 7, 41427 (2017).","journal-title":"Sci. Rep."},{"key":"1335_CR117","doi-asserted-by":"publisher","first-page":"2634","DOI":"10.1038\/s41375-022-01682-2","volume":"36","author":"ED B\u00fchrer","year":"2022","unstructured":"B\u00fchrer, E. D. et al. Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance. Leukemia 36, 2634\u20132646 (2022).","journal-title":"Leukemia"},{"key":"1335_CR118","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1002\/eji.200425442","volume":"35","author":"JI Ellyard","year":"2005","unstructured":"Ellyard, J. I., Avery, D. T., Mackay, C. R. & Tangye, S. G. Contribution of stromal cells to the migration, function and retention of plasma cells in human spleen: potential roles of CXCL12, IL\u20106 and CD54. Eur. J. Immunol. 35, 699\u2013708 (2005).","journal-title":"Eur. J. Immunol."},{"key":"1335_CR119","doi-asserted-by":"publisher","first-page":"191","DOI":"10.4049\/jimmunol.1200802","volume":"189","author":"E Umemoto","year":"2012","unstructured":"Umemoto, E. et al. Constitutive plasmacytoid dendritic cell migration to the splenic white pulp is cooperatively regulated by CCR7- and CXCR4-Mediated signaling. J. Immunol. 189, 191\u2013199 (2012).","journal-title":"J. Immunol."},{"key":"1335_CR120","doi-asserted-by":"publisher","first-page":"3889","DOI":"10.1182\/blood-2012-09-457887","volume":"121","author":"T Oellerich","year":"2013","unstructured":"Oellerich, T. et al. \u03b22 integrin\u2013derived signals induce cell survival and proliferation of AML blasts by activating a Syk\/STAT signaling axis. Blood 121, 3889\u20133899 (2013).","journal-title":"Blood"},{"key":"1335_CR121","doi-asserted-by":"publisher","first-page":"2751","DOI":"10.1038\/s41375-022-01714-x","volume":"36","author":"M Thastrup","year":"2022","unstructured":"Thastrup, M., Duguid, A., Mirian, C., Schmiegelow, K. & Halsey, C. Central nervous system involvement in childhood acute lymphoblastic leukemia: challenges and solutions. Leukemia 36, 2751\u20132768 (2022).","journal-title":"Leukemia"},{"key":"1335_CR122","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1182\/blood.2022017035","volume":"141","author":"NE Kopmar","year":"2023","unstructured":"Kopmar, N. E. & Cassaday, R. D. How I prevent and treat central nervous system disease in adults with acute lymphoblastic leukemia. Blood 141, 1379\u20131388 (2023).","journal-title":"Blood"},{"key":"1335_CR123","doi-asserted-by":"publisher","first-page":"4560","DOI":"10.1182\/bloodadvances.2021004999","volume":"5","author":"C Ganzel","year":"2021","unstructured":"Ganzel, C. et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv. 5, 4560\u20134568 (2021).","journal-title":"Blood Adv."},{"key":"1335_CR124","doi-asserted-by":"publisher","first-page":"3142","DOI":"10.1200\/JCO.2005.03.3373","volume":"24","author":"JC Barredo","year":"2006","unstructured":"Barredo, J. C. et al. Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a pediatric oncology group study. J. Clin. Oncol. 24, 3142\u20133149 (2006).","journal-title":"J. Clin. Oncol."},{"key":"1335_CR125","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1182\/blood-2006-05-018192","volume":"109","author":"AK Fielding","year":"2007","unstructured":"Fielding, A. K. et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12\/ECOG 2993 study. Blood 109, 944\u2013950 (2007).","journal-title":"Blood"},{"key":"1335_CR126","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1189\/jlb.5MA0915-394R","volume":"99","author":"TR Jost","year":"2016","unstructured":"Jost, T. R. et al. Role of CXCR4\u2010mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia. J. Leukoc. Biol. 99, 1077\u20131087 (2016).","journal-title":"J. Leukoc. Biol."},{"key":"1335_CR127","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.leukres.2018.07.001","volume":"71","author":"M M\u00e4rz","year":"2018","unstructured":"M\u00e4rz, M. et al. Pediatric acute lymphoblastic leukemia\u2014Conquering the CNS across the choroid plexus. Leuk. Res. 71, 47\u201354 (2018).","journal-title":"Leuk. Res."},{"key":"1335_CR128","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1182\/blood.2022019532","volume":"141","author":"J-M Ribera","year":"2023","unstructured":"Ribera, J.-M. T-ALL in CNS-3 status needs improvement. Blood 141, 1779\u20131780 (2023).","journal-title":"Blood"},{"key":"1335_CR129","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1038\/nature08020","volume":"459","author":"S Buonamici","year":"2009","unstructured":"Buonamici, S. et al. CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia. Nature 459, 1000\u20131004 (2009).","journal-title":"Nature"},{"key":"1335_CR130","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.1750-3639.2003.tb00005.x","volume":"13","author":"S Columba-Cabezas","year":"2003","unstructured":"Columba-Cabezas, S., Serafini, B., Ambrosini, E. & Aloisi, F. Lymphoid Chemokines CCL19 and CCL21 are Expressed in the central nervous system during experimental autoimmune encephalomyelitis: implications for the maintenance of chronic neuroinflammation. Brain Pathol. 13, 38\u201351 (2003).","journal-title":"Brain Pathol."},{"key":"1335_CR131","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.immuni.2015.12.022","volume":"44","author":"J Cupovic","year":"2016","unstructured":"Cupovic, J. et al. Central nervous system stromal cells control Local CD8+ T cell responses during virus-induced neuroinflammation. Immunity 44, 622\u2013633 (2016).","journal-title":"Immunity"},{"key":"1335_CR132","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.ccell.2019.08.001","volume":"36","author":"T O\u2019Connor","year":"2019","unstructured":"O\u2019Connor, T. et al. Age-related gliosis promotes central nervous system lymphoma through CCL19-mediated tumor cell retention. Cancer Cell 36, 250\u2013267.e9 (2019).","journal-title":"Cancer Cell"},{"key":"1335_CR133","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/nri1352","volume":"4","author":"M Thome","year":"2004","unstructured":"Thome, M. CARMA1, BCL-10 and MALT1 in lymphocyte development and activation. Nat. Rev. Immunol. 4, 348\u2013359 (2004).","journal-title":"Nat. Rev. Immunol."},{"key":"1335_CR134","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/leu.2016.272","volume":"31","author":"SR Oruganti","year":"2017","unstructured":"Oruganti, S. R. et al. CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS. Leukemia 31, 255\u2013258 (2017).","journal-title":"Leukemia"},{"key":"1335_CR135","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1080\/10428194.2021.1910684","volume":"62","author":"KL Walker","year":"2021","unstructured":"Walker, K. L. et al. CXCR4 allows T cell acute lymphoblastic leukemia to escape from JAK1\/2 and BCL2 inhibition through CNS infiltration. Leuk. Lymphoma 62, 1167\u20131177 (2021).","journal-title":"Leuk. Lymphoma"},{"key":"1335_CR136","doi-asserted-by":"publisher","first-page":"eabf7844","DOI":"10.1126\/science.abf7844","volume":"373","author":"A Cugurra","year":"2021","unstructured":"Cugurra, A. et al. Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma. Science 373, eabf7844 (2021).","journal-title":"Science"},{"key":"1335_CR137","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/s41586-022-04596-2","volume":"604","author":"T Masuda","year":"2022","unstructured":"Masuda, T. et al. Specification of CNS macrophage subsets occurs postnatally in defined niches. Nature 604, 740\u2013748 (2022).","journal-title":"Nature"},{"key":"1335_CR138","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","volume":"24","author":"M Binnewies","year":"2017","unstructured":"Binnewies, M. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24, 541\u2013550 (2017).","journal-title":"Nat. Med."},{"key":"1335_CR139","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1182\/bloodadvances.2020002832","volume":"5","author":"L Fahy","year":"2021","unstructured":"Fahy, L. et al. Hypoxia favors chemoresistance in T-ALL through an HIF1\u03b1-mediated mTORC1 inhibition loop. Blood Adv. 5, 513\u2013526 (2021).","journal-title":"Blood Adv."},{"key":"1335_CR140","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s13045-018-0554-z","volume":"11","author":"J Wang","year":"2018","unstructured":"Wang, J. et al. Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells. J. Hematol. Oncol. 11, 11 (2018).","journal-title":"J. Hematol. Oncol."},{"key":"1335_CR141","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1158\/2767-9764.CRC-23-0333","volume":"3","author":"GJ Hanna","year":"2023","unstructured":"Hanna, G. J. et al. A Phase I study of the pan-notch inhibitor CB-103 for patients with advanced adenoid cystic carcinoma and other tumors. Cancer Res. Commun. 3, 1853\u20131861 (2023).","journal-title":"Cancer Res. Commun."},{"key":"1335_CR142","doi-asserted-by":"publisher","first-page":"2630","DOI":"10.1182\/blood-2019-127121","volume":"134","author":"GL Uy","year":"2019","unstructured":"Uy, G. L. et al. CXCR4 Inhibition with BL-8040 in Combination with Nelarabine in Patients with Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia \/ Lymphoblastic Lymphoma. Blood 134, 2630 (2019).","journal-title":"Blood"},{"key":"1335_CR143","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1200\/JCO.2007.15.9319","volume":"26","author":"MQ Lacy","year":"2008","unstructured":"Lacy, M. Q. et al. Phase I, pharmacokinetic and pharmacodynamic study of the anti\u2013insulinlike growth factor Type 1 receptor monoclonal antibody CP-751,871 in patients with multiple myeloma. J. Clin. Oncol. 26, 3196\u20133203 (2008).","journal-title":"J. Clin. Oncol."},{"key":"1335_CR144","doi-asserted-by":"publisher","first-page":"2730","DOI":"10.1158\/1078-0432.CCR-14-3090","volume":"21","author":"M Hansson","year":"2015","unstructured":"Hansson, M. et al. A Phase I dose-escalation study of antibody BI-505 in relapsed\/refractory multiple myeloma. Clin. Cancer Res. 21, 2730\u20132736 (2015).","journal-title":"Clin. Cancer Res."},{"key":"1335_CR145","doi-asserted-by":"publisher","first-page":"753","DOI":"10.4049\/jimmunol.2200635","volume":"210","author":"N Poirier","year":"2023","unstructured":"Poirier, N. et al. First-in-human study in healthy subjects with the noncytotoxic monoclonal antibody OSE-127, a strict antagonist of IL-7R\u03b1. J. Immunol. 210, 753\u2013763 (2023).","journal-title":"J. Immunol."},{"key":"1335_CR146","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1038\/s41375-019-0434-8","volume":"33","author":"P Akkapeddi","year":"2019","unstructured":"Akkapeddi, P. et al. A fully human anti-IL-7R\u03b1 antibody promotes antitumor activity against T-cell acute lymphoblastic leukemia. Leukemia 33, 2155\u20132168 (2019).","journal-title":"Leukemia"},{"key":"1335_CR147","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41375-019-0531-8","volume":"34","author":"JA Hixon","year":"2020","unstructured":"Hixon, J. A. et al. New anti-IL-7R\u03b1 monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models. Leukemia 34, 35\u201349 (2020).","journal-title":"Leukemia"},{"key":"1335_CR148","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1182\/blood.2023021088","volume":"143","author":"L Lenk","year":"2024","unstructured":"Lenk, L. et al. The IL-7R antagonist lusvertikimab reduces leukemic burden in xenograft ALL via antibody-dependent cellular phagocytosis. Blood 143, 2735\u20132748 (2024).","journal-title":"Blood"},{"key":"1335_CR149","doi-asserted-by":"publisher","first-page":"3510","DOI":"10.1182\/blood-2012-03-415448","volume":"120","author":"SL Maude","year":"2012","unstructured":"Maude, S. L. et al. Targeting JAK1\/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood 120, 3510\u20133518 (2012).","journal-title":"Blood"}],"container-title":["Experimental &amp; Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s12276-024-01335-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s12276-024-01335-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s12276-024-01335-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T11:02:53Z","timestamp":1733137373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s12276-024-01335-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,1]]},"references-count":149,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["1335"],"URL":"https:\/\/doi.org\/10.1038\/s12276-024-01335-7","relation":{},"ISSN":["2092-6413"],"issn-type":[{"value":"2092-6413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,1]]},"assertion":[{"value":"6 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}