Unraveling MLL1-fusion leukemia: Epigenetic revelations from an iPS cell point mutation.

ABSTRACT: Our understanding of acute leukemia pathology is heavily dependent on 11q23 chromosomal translocations involving the mixed lineage leukemia-1 (MLL1) gene, a key player in histone H3 lysine 4 (H3K4) methylation. These translocations result in MLL1-fusion (MLL1_F) proteins that are thought to drive leukemogenesis. However, the mechanism behind increased H3K4 trimethylation in MLL1_F-leukemic stem cells (MLL1_F-LSCs), following loss of the catalytic SET domain of MLL1 (known for H3K4 monomethylation and dimethylation) remains unclear. In our investigation, we introduced a homozygous loss-of-function point mutation in MLL1 within human-induced pluripotent stem cells. This mutation mimics the histone methylation, gene expression, and epithelial-mesenchymal transiti

SUBMITTER: Kobrossy L 

PROVIDER: S-EPMC11541820 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature