METTL3 mediates bone marrow mesenchymal stem cell adipogenesis to promote chemoresistance in acute myeloid leukaemia

FEBS Open Bio

Xiao‐ting Wang¹  Di‐yu Hou¹  Hui‐fang Huang¹  Ruo‐lan You¹  Zhi‐peng Pan¹  Bin Wang²  Wen‐hui Xie³ 

[1] Central Laboratory, Fujian Medical University Union Hospital, China;Central Laboratory, Fujian Medical University Union Hospital, China;Clinical Laboratory, Fujian Maternal and Child Health Hospital, Fujian Children's Hospital, China;Graduate School, Fujian Medical University, Fujian Medical University Union Hospital, China;

关键词: adipogenesis;    AML;    chemoresistance;    mA;    MSCs;   

DOI  :  10.1002/2211-5463.13165

来源: Wiley

【 摘 要 】

Adipogenesis of bone marrow mesenchymal stem cells (MSCs) promotes chemoresistance of acute myeloid leukaemia (AML) cells. MSCs from AML patients (AML‐MSCs) display enhanced adipogenesis compared with bone marrow MSCs from healthy donors. However, the precise molecular mechanism by which adipogenesis of MSCs from AML marrow differs from normal counterparts remains obscure. We found that METTL3 significantly inhibits MSC adipogenesis. Here, we aimed to identify the molecular mechanism linking METTL3 and MSC adipogenesis. Analysis of m6A epigenetic changes in MSCs determined via RIP‐qPCR and MeRIP‐qPCR indicated that METTL3 affects AKT protein expression in MSCs by mediating m6A modification of AKT1‐mRNA. Downregulated METTL3 expression in AML‐MSCs induced an increase in AKT protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in AML cells. Therefore, targeting AKT regulation by mRNA modification in MSC adipogenesis might provide a novel therapeutic strategy to overcome AML chemoresistance.

【 授权许可】

CC BY