Leukemia mutated proteins PHF6 and PHIP form a chromatin complex that represses acute myeloid leukemia stemness.

ABSTRACT: Myeloid leukemias are heterogeneous cancers with diverse mutations, sometimes in genes with unclear roles and unknown functional partners. PHF6 and PHIP are two poorly understood chromatin-binding proteins recurrently mutated in acute myeloid leukemia (AML). PHF6 mutations are associated with poorer outcomes, whereas PHIP was recently identified as the most common selective mutation in Black patients with AML. Here, we show that Phf6 knockout converts Flt3-ITD-driven mouse chronic myelomonocytic leukemia (CMML) into AML with reduced survival. Using cell line models, we show that PHF6 is a transcriptional repressor that suppresses a limited stemness gene network and that PHF6 missense mutations, classified by current clinical algorithms as variants of unkn

SUBMITTER: Pawar AS 

PROVIDER: S-EPMC12340699 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature