Acute myeloid leukemia (AML)-derived bone mesenchymal stem cell exosomal METTL14 promotes AML cell growth and glycolysis by HOXA3/WNT7B axis.

Acute myeloid leukemia (AML)-derived bone mesenchymal stem cell (MSC) exosomes have been confirmed to have a positive effect on AML progression. This study aim to reveal the underlying molecular mechanism by which AML-MSC-derived exosomes promotes AML progression. AML-MSC was isolated from the bone marrow aspirates of AML patients. After incubated with AML-MSC, AML cell functions were analyzed. The expression levels of methyltransferase-like 14 (METTL14), homeobox A3 (HOXA3), WNT family member 7B (WNT7B) and glycolysis-related markers were examined. Exosomes were isolated from AML-MSC and then the obtained exosomes were co-cultured with AML cells. AML-MSC co-culturing could enhance AML cell proliferation and glycolysis, while repress cell apoptosis. METTL14 was upregulated in exosomes from AML-MSC, which could be ingested by AML cells. METTL14 could enhance HOXA3 mRNA stability via promoting its m6A modification. Knockdown of exosomal METTL14 from AML-MSC inhibited AML cell growth and glycolysis, while were reversed by HOXA3. In addition, HOXA3 bound to WNT7B promoter to increase its transcription, and WNT7B overexpression also eliminated si-HOXA3-mediated inhibitory on AML cell growth and glycolysis. Animal study revealed that knockdown of exosomal METTL14 from AML-MSC reduced AML tumorigenesis by decreasing HOXA3 and WNT7B expression. AML-MSC-derived exosomal METTL14 facilitated AML cell growth and glycolysis by activating the HOXA3/WNT7B axis, providing a new mechanism for understanding AML-MSC-derived exosomes to promote AML progression.