New Insights into the Diverse Functions of the Blood Cancer Gene DNMT3A

Recent research has revealed unexpected roles of the gene DNMT3A, previously known primarily for its involvement in blood cell development. This gene is crucial for guiding hematopoietic stem cells—the foundation for all blood cell types such as red blood cells, white blood cells, and platelets—into their proper functions. Mutations in DNMT3A, often associated with aging or environmental factors like smoking, are known to elevate the risk of blood cancers, including acute myeloid leukemia (AML). Traditionally, DNMT3A was understood to influence gene activity through a process called DNA methylation, where chemical tags are added to DNA molecules. However, emerging evidence indicates that DNMT3A possesses additional, methylation-independent functions affecting blood stem cell health and stability.

A groundbreaking study led by Grant A. Challen at WashU Medicine, published in Cell Stem Cell, demonstrates that DNMT3A also impacts the length of telomeres—the protective caps at the ends of DNA strands that shorten as cells divide. Loss or dysfunction of DNMT3A results in longer telomeres, which remove the natural limits on cell division and enable blood stem cells to multiply excessively, a hallmark characteristic of cancer. Furthermore, the research uncovered new roles for DNMT3A in DNA damage response mechanisms, essential processes that maintain genome integrity and influence cancer development and progression.

This research, conducted in both mouse models and human cells, broadens our understanding of how DNMT3A contributes to blood cancer biology. These insights may pave the way for developing novel therapeutic approaches targeting these newly identified functions of the gene. For more details, the study can be accessed via DOI: 10.1016/j.stem.2025.06.010.

Source: https://medicalxpress.com/news/2025-09-roles-blood-cancer-gene-dnmt3a.html