Acute myeloid leukemia (AML) patients with DNA methyltransferase 3A (DNMT3A) mutations in remission after induction chemotherapy may have hematopoiesis arising from a putative pre-leukemic clone lacking the full spectrum of mutations seen at AML diagnosis. DNMT3A mutations in hematopoietic stem cells lead to increased self-renewal capacity and dominance of the stem-cell compartment. The common DNMT3AR882H mutation is usually heterozygous and results in loss-of-function with a dominant-negative effect. DNMT3A mutations are thought to occur early in AML ontogeny, and are found in around 20% of de novo AML and in a higher proportion of secondary AML cases. In population studies clonal mutations of DNMT3A6 and other epigenetic regulators are more common with increasing age, and may contribute to a proportion of cases of age-related skewing of X-chromosome inactivation.
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- Acute myeloid leukemia