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Despite advances in chemotherapy and targeted therapies, drug resistance and high relapse rates remain the major challenges in AML treatment. Accumulating evidence indicates that bone marrow mesenchymal stem cells (MSCs)-mediated microenvironment changes play a crucial role in the pathogenesis of AML and may contribute to the therapeutic challenges of current treatment strategies. In this study, we further characterized the role and revealed the molecular mechanism of AML-derived MSCs (AML-MSCs) in AML pathogenesis. We found that AML-MSCs significantly promoted AML cell proliferation and inhibited apoptosis, primarily through direct cell-to-cell contact. Bioinformatics analysis of multiple sequencing datasets revealed that decorin (DCN), encoding a core extracellular matrix protein, is significantly upregulated in AML-MSCs. DCN could enhance AML cell viability through functional interplay with matrix metalloproteinase-2 (MMP2) in AML cells. Both inhibition of DCN in AML-MSCs and MMP2 in AML cells significantly attenuated the supportive effect of AML-MSCs on AML cells. These findings provide novel insights into the role of MSC-mediated bone marrow microenvironment remodeling in AML pathogenesis and highlight DCN and MMP2 as potential therapeutic targets for AML treatment.<\/jats:p>","DOI":"10.1177\/15473287251405391","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T08:28:15Z","timestamp":1766996895000},"page":"35-45","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Bone Marrow Mesenchymal Stem Cells Derived from Acute Myeloid Leukemia Patients Contribute to Leukemia Cell Survival Through Decorin\/Matrix Metalloproteinase-2 Crosstalk"],"prefix":"10.1177","volume":"35","author":[{"given":"Xianning","family":"Zhang","sequence":"first","affiliation":[{"name":"Medical Research Center, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 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