Chronic Myeloid Leukemia (CML) is a malignant myeloproliferative disease caused by a chromosomal translocation that produces the constitutively activated tyrosine kinase BCR-ABL1 fusion protein. Tyrosine kinase inhibitors (TKIs) are the first-choice treatment. However, resistance to TKIs remains a challenge for curing CML patients. To gain insight into the role of m6A modification in CML, we analyze the role of the METTL3/METTL14 m6A writing complex in the BCR-ABL1+ K562 CML cellular model. We show that knockdown of METTL3 and METTL14 strongly impaired proliferation of both TKI-sensitive and TKI-resistant cells. Furthermore, we demonstrate that MYC oncogenes is highly m6A methylated in CML and that m6A marks are required for its efficient expression. Therefore, our findings demonstrate an important role for m6A methylation in CML and show that targeting the METTL3/METTL14 complex may represent a promising therapeutic strategy for TKIs resistant CML cells
