Mesenchymal stem cells-like as a prognostic biomarker in patients diagnosed with acute myeloid leukemia

The bone marrow microenvironment influences acute myeloid leukemia (AML) progression. Mesenchymal stem cell-like (MSC-l) populations may exert tumor-modulating effects, but their prognostic role remains uncertain. We retrospectively analyzed 65 adult AML patients (excluding acute promyelocytic leukemia) treated with intensive chemotherapy between 2017 and 2024 at four Spanish institutions. MSC-l cells were identified in BM aspirates at end of treatment by multiparameter flow cytometry (CD13^bright/CD45^low/CD34^neg/CD117^neg/CD11b^neg/CD16^neg/CD71^neg/CD64^neg). Patients were stratified using a 0.265%cutoff (MSC-l^HIGH ≥ 0.265% and MSC-l^LOW < 0.265%). Survival was assessed with Kaplan-Meier and Cox regression, adjusting for age and ELN 2017 risk. MSC-l^HIGH patients had inferior overall survival (OS) (median 0.66 years vs. not reached; P < 0.001) and relapse-free survival (RFS) (median 1.27 years vs. 1.49 years; P = 0.027). These associations persisted across ELN risk groups. Multivariate analysis confirmed MSC-l^HIGH status as an independent predictor of worse OS (HR = 6.43; 95% CI 2.53-16.33; P < 0.001) and RFS (HR = 4.8; 95% CI 1.71-13.47; P = 0.003). MSC-l levels were lower in patients receiving myeloablative conditioning compared with non-transplanted patients, suggesting transplant intensity may influence MSC dynamics. Higher post-treatment MSC-l proportions are associated with poorer survival, independent of ELN risk and age, supporting their potential as a prognostic biomarker in AML.