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

Abstract The bone marrow (BM) microenvironment plays a pivotal role in acute myeloid leukemia (AML) progression. Among its components, mesenchymal stem cells (MSCs) can exhibit tumor-modulating properties, yet their precise prognostic significance in AML remains unclear. To evaluate the prognostic impact of MSC-like (MSC-l) cells in adult AML patients treated with intensive chemotherapy. We retrospectively analyzed 65 adult AML patients (excluding acute promyelocytic leukemia) treated between 2017 and 2024 at four spanish institutions. MSC-l cells were identified in BM aspirates at the end of treatment by multiparameter flow cytometry as CD13bright/CD45low/CD34neg/CD117neg/CD11bneg/CD16neg/CD71neg/CD64neg. Patients were stratified based on MSC-l proportion using a cut-off of 0.265% (MSC-lHIGH patients ˃0265% and MSC-lLOW patients ≤ 0.265%). Survival outcomes were assessed using Kaplan-Meier and Cox regression analyses, adjusting for age and ELN 2017 risk classification. MSC-lHIGH patients showed significantly reduced overall survival (OS) (median OS: 0.66 years vs. not calculable; P < 0.001) and relapse-free survival (RFS) (median RFS: 1.27 vs. 1.49 years; P = 0.027) compared to MSC-lLOW patients. Stratified analyses confirmed this trend across ELN 2017 risk groups. Multivariate Cox regression identified MSC-lHIGH status as an independent predictor of worse OS (HR = 11.68, 95% CI: 3.80–35.9, P < 0.01) and RFS (HR = 3.38, 95% CI: 1.15–9.96, P = 0.03). A higher proportion of MSC-l cells at end of treatment is associated with inferior survival outcomes in AML, independent of ELN risk and age. These findings suggest that MSC-l quantification may provide additional prognostic value and warrant validation in prospective studies.