DOI: 10.11958/20240355
T-ALL derived bone marrow stromal stem cells promote T-ALL proliferation through the FGF2-FGFR2 pathway
YANG Jian
LI Min
LI Yueyang
TIAN Chen
Abstract：Objective To elucidate the mechanistic role of bone marrow mesenchymal stromal cells(BM-MSCs)in T-cell acute lymphoblastic leukemia(T-ALL),and to find effective therapeutic strategies targeting BM-MSCs.Methods A T-ALL mouse model induced by Notch-1 overexpression was constructed.An in vitro co-culture system was established to investigate the proliferative capacity of T-ALL cells upon co-culturing with leukemia-derived MSCs.RNA sequencing was performed to identify key differentially expressed genes,which were further validated by PCR.BGJ398 was injected into mice to detect tumor growth.Results Co-culturing with T-ALL-derived MSCs resulted in a significant increase in T-ALL cell proliferation.RNA sequencing results revealed that the secretion of fibroblast growth factor 2(FGF2)from T-ALL-derived MSCs was increased,which binds to fibroblast growth factor 2 receptor(FGFR2)on T-ALL cells,activating the PI3K/AKT/mTOR signaling pathway.Blocking the interaction between FGF2 and FGFR2 using BGJ398 inhibited the growth of T-ALL tumors in mice.Conclusion BM-MSCs can promote T-ALL tumor growth through FGF2/FGFR2 pathway,and blocking FGF2/FGFR2 pathway is an effective strategy to overcome BM-MSCS-mediated T-ALL progression.
Keywords：precursor cell lymphoblastic leukemia-lymphomafibroblast growth factor 2cell proliferationbone marrow mesenchymal stromal cellsBGJ398
Publication Date：2025-01-14
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 29-34 )