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The current study aimed to understand the dynamic interplay between AML-BM-MSC and their soluble factors in determining the fate of AML blasts within the microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>AML-BM-MSC were cultured and characterized for expression of phenotyping markers, multilineage differentiation potential, and gene expression analysis by microarray. To understand cross talk, AML-BM-MSC were co-cultured with the AML cell line OCI-AML2 and assessed for changes in cell cycle phases, mitochondrial activity, and cytarabine-induced cell death. Differential regulation of AML blast fate was evaluated by conducting co-culture experiments with cell-free-conditioned media (PD-MSC-CM) and in the presence of cell\u2013cell contact of AML-BM-MSC. Further, PD-MSC-CM was assessed in vivo for tumor reduction potential using a leukemia xenograft model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Besides standard features, AML-BM-MSC exhibited increased vesicles, MSC bodies (exosomes), and mitochondria. Altered AML-BM-MSC demonstrated upregulation of inflammasome pathway markers in microarray, which was further validated by ELISA and quantitative real-time polymerase chain reaction. Co-culture experiments on AML-BM-MSC revealed protective effects on AML blasts in the presence of cytarabine. In contrast, PD-MSC-CM significantly inhibited AML cell growth alone and synergistically with cytarabine. Further, PD-MSC-CM significantly reduced tumor growth in the leukemia mouse model, and this effect was mediated by regulation of the NLRP3 inflammasome pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Summarizing, the leukemic blasts and AML-MSC in the BM microenvironment interact differentially in cell\u2013cell contact compared to only soluble factors. Further, our study has provided innovative leads that PD-MSC-CM effectively abrogates leukemia tumor growth, enhances chemosensitivity and can be developed further as an immunomodulatory novel \"off-the-shelf\" therapeutic agent for leukemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00262-025-04262-2","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T12:43:03Z","timestamp":1771850583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defining alteration in bone marrow mesenchymal stem cells (MSC) from acute myeloid leukemia and exploring cultured MSC-conditioned media as a novel anti-leukemia therapy agent"],"prefix":"10.1007","volume":"75","author":[{"given":"Manasi","family":"Nagare","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monalisa","family":"Sahoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manju","family":"Sengar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin","family":"Punatar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Navin","family":"Khattry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anant","family":"Gokarn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhausaheb","family":"Bagal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hasmukh","family":"Jain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumeet","family":"Mirgh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sridhar","family":"Epari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanuja","family":"Shet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trupti","family":"Pradhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shweta","family":"Shirsat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madan","family":"Barkume","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Mathen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poonam","family":"Gera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohit Kumar","family":"Verma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elveera","family":"Saldanha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pratik","family":"Chandrani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jitendra","family":"Gawde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shubhada","family":"Chiplunkar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyoti","family":"Kode","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"issue":"4","key":"4262_CR1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.21037\/atm-23-1824","volume":"12","author":"AP Urs","year":"2024","unstructured":"Urs AP, Goda C, Kulkarni R (2024) Remodeling of the bone marrow microenvironment during acute myeloid leukemia progression. 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