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The aggressiveness of particular B\u2010ALL subtypes could be related to specific mechanisms used to reprogram bone marrow stromal cells. The purpose of this study is to compare the effect of two B\u2010ALL subtypes, with opposite prognosis, on mesenchymal stem cells (MSC) functions and the consequences on leukemic cell properties. We have established an in vitro leukemic niche (LN) by co\u2010culturing MSC with REH (favorable prognosis) or SUP\u2010B15 (poor prognosis) B\u2010ALL cell lines and examined leukemic\u2010induced MSC reprogramming and its impact on leukemic cells properties and drug resistance. The aggressive SUP\u2010B15 cell line showed faster and stronger adherence to MSC and increased migration to CXCL12 and LN secretome, compared to REH cells. SUP\u2010B15 cell proliferation was reduced but modulated over time. No differences in MSC senescence induction or recovery were observed between both cell lines. Interestingly, the SUP\u2010B15 LN secretome was enriched in IL\u20106, IL\u20108, CCL2 and MIF. MSC pre\u2010incubated with CCL2 showed increased MSC senescence but this did not alter protection against cytotoxic drugs. On the contrary, MSC self\u2010renewal and adipogenic differentiation were also increased in the aggressive SUP\u2010B15 cell line, strengthening protection against the cytotoxic drugs vincristine, methotrexate and doxorubicin. This study showed that the aggressiveness of certain leukemia subtypes is also associated with specific changes induced in MSC secretome and stemness that have an impact on specific properties of leukemic cells, improving LN fitness and ability to survive to cytotoxic drugs.<\/jats:p>","DOI":"10.1002\/ccs3.70009","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T21:29:49Z","timestamp":1749763789000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Favorable and poor prognosis B\u2010cell precursor acute lymphoblastic leukemia subtypes reveal distinct leukemic cell properties when interacting with mesenchymal stem cells, differentially modifying their cell stemness and leukemia chemoresistance"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4664-8237","authenticated-orcid":false,"given":"Santiago","family":"\u00c1ngel 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