Remethylation of Dnmt3a^-/- hematopoietic cells is associated with partial correction of gene dysregulation and reduced myeloid skewing.

ABSTRACT: Mutations in the DNA methyltransferase 3A (DNMT3A) gene are the most common cause of age-related clonal hematopoiesis (ARCH) in older individuals, and are among the most common initiating events for acute myeloid leukemia (AML). The most frequent DNMT3A mutation in AML patients (R882H) encodes a dominant-negative protein that reduces methyltransferase activity by ∼80% in cells with heterozygous mutations, causing a focal, canonical DNA hypomethylation phenotype; this phenotype is partially recapitulated in murine Dnmt3a^-/- bone marrow cells. To determine whether the hypomethylation phenotype of Dnmt3a^-/- hematopoietic cells is reversible, we developed an inducible transgene to restore expression of DNMT3A in transplanted bone

SUBMITTER: Ketkar S 

PROVIDER: S-EPMC7022185 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature