The Role of N(6)-Methyladenosine (m(6)A) Methylation Modifications in Hematological Malignancies

SIMPLE SUMMARY: Recently, despite the common application of various novel therapies (e.g., immunotherapy and stem cell transplantation) in hematologic tumors, hematologic malignancies remain suboptimal and have a worse prognosis due to the lack of donors and their high heterogeneity. Among them, epigenetic alterations (e.g., the abnormal modification of m(6)A) are essential to facilitate the progression of tumors and drug resistance. Our purpose in this study is to pinpoint the molecular targets of pathogenesis, as well as to analyze the oncogenic characteristics of m(6)A modifications. In this article, we, therefore, elaborate on the mechanisms of m(6)A modification and its role in normal hematopoietic regulation and malignant tumorigenesis, thus contributing to the refinement of molecularly targeted therapies. ABSTRACT: Epigenetics is identified as the study of heritable modifications in gene expression and regulation that do not involve DNA sequence alterations, such as DNA methylation, histone modifications, etc. Importantly, N(6)-methyladenosine (m(6)A) methylation modification is one of the most common epigenetic modifications of eukaryotic messenger RNA (mRNA), which plays a key role in various cellular processes. It can not only mediate various RNA metabolic processes such as RNA splicing, translation, and decay under the catalytic regulation of related enzymes but can also affect the normal development of bone marrow hematopoiesis by regulating the self-renewal, proliferation, and differentiation of pluripotent stem cells in the hematopoietic microenvironment of bone marrow. In recent years, numerous studies have demonstrated that m(6)A methylation modifications play an important role in the development and progression of hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndromes [MDS], multiple myeloma [MM], etc.). Targeting the inhibition of m(6)A-associated factors can contribute to increased susceptibility of patients with hematologic malignancies to therapeutic agents. Therefore, this review elaborates on the biological characteristics and normal hematopoietic regulatory functions of m(6)A methylation modifications and their role in the pathogenesis of hematologic malignancies.