DNMT3A^R882H Is Not Required for Disease Maintenance in Primary Human AML, but Is Associated With Increased Leukemia Stem Cell Frequency.

ABSTRACT: Genetic mutations are being thoroughly mapped in human cancers, yet a fundamental question in cancer biology is whether such mutations are functionally required for cancer initiation, maintenance of established cancer, or both. Here, we study this question in the context of human acute myeloid leukemia (AML), where DNMT3A ^R882 missense mutations often arise early, in pre-leukemic clonal hematopoiesis, and corrupt the DNA methylation landscape to initiate leukemia. We developed CRISPR-based methods to directly correct DNMT3A ^R882 mutations in leukemic cells obtained from patients. Surprisingly, DNMT3A ^R882 mutations were largely dispensable for disease maintenance. Replacing DNMT3A ^R882 mutan

SUBMITTER: Kohnke T 

PROVIDER: S-EPMC11565803 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature