{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:52:33Z","timestamp":1772164353470,"version":"3.50.1"},"reference-count":49,"publisher":"American Association for Cancer Research (AACR)","issue":"14","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The importance of microenvironmental factors for driving progression in leukemia has been debated. Previous evidence has pointed to interleukin-7 (IL-7), a fundamental cytokine to normal T-cell development and homeostasis, as an important determinant of the viability and proliferation of T-cell acute lymphoblastic leukemia (T-ALL) cells in vitro. In this study, we report that IL-7 is also a critical determinant of T-ALL progression. T-ALL cell lines and primary T-ALL samples initiated leukemia more slowly when engrafted to immunocompromised Rag2\u2212\/\u2212IL2rg\u2212\/\u2212 mice lacking IL-7. This effect was not related to reduced engraftment or homing of transplanted cells to the bone marrow. Instead, IL-7 deficiency diminished expansion of leukemia cells in the bone marrow and delayed leukemia-associated death of transplanted mice. Moreover, infiltration of different organs by T-ALL cells, which characterizes patients with advanced disease, was more heterogeneous and generally less efficient in IL-7\u2013deficient mice. Leukemia progression was associated with increased Bcl-2 expression and cell viability, reduced p27Kip1 expression, and decreased cell-cycle progression. Clinical measurements of IL-7 plasma levels and IL-7 receptor (IL-7R) expression in T-ALL patients versus healthy controls confirmed that IL-7 stimulates human leukemia cells. Our results establish that IL-7 contributes to the progression of human T-cell leukemia, and they offer preclinical validation of the concept that targeting IL-7\/IL-7R signaling in the tumor microenvironment could elicit therapeutic effects in T-ALL. Cancer Res; 71(14); 4780\u20139. \u00a92011 AACR.<\/jats:p>","DOI":"10.1158\/0008-5472.can-10-3606","type":"journal-article","created":{"date-parts":[[2011,5,18]],"date-time":"2011-05-18T23:07:30Z","timestamp":1305760050000},"page":"4780-4789","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":120,"title":["IL-7 Contributes to the Progression of Human T-cell Acute Lymphoblastic Leukemias"],"prefix":"10.1158","volume":"71","author":[{"given":"Ana","family":"Silva","sequence":"first","affiliation":[{"name":"Authors' Affiliations:\u20081Instituto de Medicina Molecular, Faculdade de Medicina da Univer, Lisbon; 2Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal; 3Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom; and 4Laborat\u00f3rio de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP, Brazil"},{"name":"Authors' Affiliations:\u20081Instituto de Medicina Molecular, Faculdade de Medicina da Univer, Lisbon; 2Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal; 3Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom; and 4Laborat\u00f3rio de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP, Brazil"}]},{"given":"Angelo B.A.","family":"Laranjeira","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Instituto de Medicina Molecular, Faculdade de Medicina da Univer, Lisbon; 2Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal; 3Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom; and 4Laborat\u00f3rio de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP, Brazil"}]},{"given":"Leila R.","family":"Martins","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Instituto de Medicina Molecular, Faculdade de Medicina da Univer, Lisbon; 2Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal; 3Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom; and 4Laborat\u00f3rio de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP, Brazil"}]},{"given":"Bruno A.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Instituto de Medicina Molecular, Faculdade de Medicina da Univer, Lisbon; 2Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal; 3Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom; and 4Laborat\u00f3rio de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP, Brazil"}]},{"given":"Jocelyne","family":"Demengeot","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Instituto de Medicina Molecular, Faculdade de Medicina da Univer, Lisbon; 2Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal; 3Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom; and 4Laborat\u00f3rio de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP, Brazil"}]},{"given":"J. Andr\u00e9s","family":"Yunes","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Instituto de Medicina Molecular, Faculdade de Medicina da Univer, Lisbon; 2Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal; 3Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom; and 4Laborat\u00f3rio de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP, Brazil"}]},{"given":"Benedict","family":"Seddon","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Instituto de Medicina Molecular, Faculdade de Medicina da Univer, Lisbon; 2Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal; 3Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom; and 4Laborat\u00f3rio de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP, Brazil"}]},{"given":"Jo\u00e3o T.","family":"Barata","sequence":"additional","affiliation":[{"name":"Authors' 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