Unraveling the function of m6A modification in acute myeloid leukemia

N6-methyladenosine (m6A) is a well-known RNA modification that can affect mRNA stability and translation (Yue et al., Genes Dev. 2015). In mammals, the m6A writer is a multicomponent complex composed of the two methyltransferases METTL3 and METTL14 and the regulatory protein WTAP. WTAP has been recently described as an oncogenic factor in AML suggesting that m6A modification might play crucial role in leukemogenesis (Bansal et al., Leukemia 2014). Notably, we also found that METTL3 and METTL14 are upregulated in primary AML samples. Here, we analyzed the functional role of m6A during myeloid differentiation of AML cell lines. Impairing the expression of the methylation complex components by RNAi affected consistently myeloid differentiation and induced massive apoptosis. Moreover, in AML cell lines METTL3 mislocalized in the cytoplasm and associated with polysomes. These data indicate that the misregulation of m6A methylation may contribute to leukemogenesis, but also highlight a putative m6A-independent role for METTL3. Our data also pave the way to the development of new therapies for AML through the inhibition of the methylome complex.