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Roles of DNA methyltransferases in hematopoiesis and hematologic malignancies
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DOI：10.1016/j.gendis.2026.102383.png)
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Abstract
En 中文
DNA methylation is a fundamental epigenetic modification in mammals. It regulates gene transcription and plays a pivotal role in governing the homeostasis and differentiation of the hematopoietic system. DNA methyltransferases (DNMTs) constitute an evolutionarily conserved family of enzymes that catalyze the transfer of a methyl group to the fifth carbon of cytosine residues. In mammals, three catalytically active DNMTs have been characterized: DNMT1, DNMT3A, and DNMT3B. DNMT3A and DNMT3B are primarily responsible for establishing de novo methylation patterns, whereas DNMT1 preserves these patterns during DNA replication. The correct regulation of DNMT activity is vital for normal hematopoietic development, whereas their dysregulation or mutation leads to profound epigenetic alterations that drive the pathogenesis of hematologic malignancies. This review first outlines the fundamental mechanisms through which DNMTs regulate DNA methylation and their roles in hematopoietic stem cell development and lineage fate decision. We then examine the emerging evidence of DNMT dysregulation in leukemia and lymphoma, highlighting their implications for disease biology and therapeutic targeting. In addition, we summarize current insights into the oncogenic potential of DNMT mutations and their cooperation with transcriptional regulators to silence tumor suppressor pathways. We then delve into recent research illustrating DNMT3B's dual role in specific hematologic contexts, underscoring the complexity of DNMT function in malignancy. Finally, we review the development of current DNMT inhibitors and their application in clinical trials, providing a broader context for understanding therapeutic challenges and future treatment directions.
Keywords:
DNA Methyltransferases
Gene Regulation
Leukemia
Lymphoma
Oncogene
Tumor Suppressor
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