Paediatric Bone marrow Mesenchymal Stem cells support acute myeloid leukaemia cell survival and enhance chemoresistance via contact-independent mechanism

Pediatric mesenchymal stem cells (pMSCs) within the bone marrow (BM) niche play a crucial role in regulating pediatric acute myeloid leukemia (pAML) survival and therapy resistance. In this study, we isolated pMSCs from pAML bone marrow samples and characterized their phenotype and differentiation potential. We performed coculture experiments with pAML cells in both autologous and allogenic settings, with and without direct contact. RNA-sequencing and multiplex immunoassays revealed that pMSCs promote pAML survival through changes in gene expression, cytokine secretion, and extracellular matrix (ECM) components, specifically enhancing chemoprotection from cytarabine and Gemtuzumab Ozogamicin (GO). Inhibition of the JAK/STAT and ERK pathways using ruxolitinib (RUX) abrogated the pMSC-induced chemoprotection, suggesting a contact-independent mechanism. These findings provide new insights into how the BM microenvironment contributes to therapy resistance in pediatric AML and highlights the potential for targeting pMSC-induced signaling pathways in treatment strategies.