N6-methyladenosine (m6A) RNA modification in chronic myeloid leukemia: unveiling a novel therapeutic target

Author:

Fernandez Rodriguez Guillermo,Tarullo Marco,Fatica AlessandroORCID

Abstract

AbstractN6-methyladenosine (m6A), the most prevalent internal mRNA modification, plays a critical role in physiological processes by regulating gene expression through modulation of mRNA metabolism at multiple stages. In recent years, m6A has garnered significant attention for a deeper understanding of the initiation, progression, and drug resistance of various cancers, including hematological malignancies. Dysregulation of m6A has been implicated in both cancer promotion and suppression. m6A methylation is a complex regulatory process involving methyltransferases (writers), demethylases (erasers), and proteins that recognize specific m6A modifications (readers). This intricate interplay presents challenges for precisely modulating m6A levels, either globally or at specific sites. This review specifically focuses on the role of m6A in chronic myeloid leukemia (CML), a blood cancer characterized by the BCR-ABL1 fusion. We emphasize its impact on leukemia cell survival and drug resistance mechanisms. Notably, inhibitors targeting m6A regulators show promise in preclinical models, suggesting a potential therapeutic avenue for CML. Integrating our understanding of m6A biology with current treatment strategies may lead to more effective therapies, especially for patients with advanced-stage or resistant CML.

Publisher

Springer Science and Business Media LLC

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