ArticleBalkan medical journal2025
Fat Mass and Obesity-Associated Protein-Mediated Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Promotes Chemotherapy Resistance in Acute Myeloid Leukemia
Article in Balkan medical journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Chemotherapy resistance and relapse in acute myeloid leukemia (AML) are associated with poor prognosis. Bone marrow mesenchymal stem cells (MSCs) show enhanced adipogenic differentiation in AML, which may contribute to chemoresistance; however, the underlying mechanisms remain incompletely understood. Aims: To investigate how adipogenic differentiation of MSCs from chemotherapy-resistant AML patients (CR-AML-MSCs) promotes chemoresistance, focusing on the roles of the fat mass and obesity-associated protein (FTO) and the mTORC1 pathway. Study Design: Experimental study. Methods: This study compared bone marrow MSCs from chemotherapy-sensitive (CS) and CR AML patients. Adipogenic differentiation was assessed using Oil Red O staining. RNA sequencing, Quantitative real-time PCR (qPCR), and western blotting were employed to analyze expression of FTO, Raptor, and PPARγ. Global N6-methyladenosin (m6A) levels were measured, and co-culture models with AML cell lines (U937, HL-60, THP-1) were established to evaluate chemoresistance. Gain- and loss-of-function experiments for FTO were performed using lentiviral overexpression and shRNA knockdown. mTORC1 pathway involvement was tested using rapamycin. Statistical analyses included t-tests and ANOVA, with significance set at ( Results: CR-AML-MSCs exhibited significantly enhanced adipogenic differentiation ( Conclusion: FTO enhances adipogenic differentiation of CR-AML-MSCs through m
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