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, while PHIP was recently identified as the most common selective mutation in Black patients in AML. Here, we show that PHF6 is a transcriptional repressor that suppresses a stemness gene network, and that PHF6 missense mutations, classified by current clinical algorithms as variants of unknown significance, produce unstable or non-functional protein. We present multiple lines of evidence converging on a critical mechanistic connection between PHF6 and PHIP. We show that P

SUBMITTER: Pawar AS 

PROVIDER: S-EPMC11642813 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature