Developmental Stage and Cellular Context Determine Oncogenic and Molecular Outcomes of <i>Ezh2</i> ^Y641F Mutation in Hematopoiesis.

ABSTRACT: Mutations in the histone methyltransferase EZH2, particularly the Y641 hotspot mutation, have been implicated in hematologic malignancies, yet the effect of timing and cellular context on their oncogenic potential has remained unknown. In this study, we utilized a conditional allele with tissue-specific Cre drivers to investigate the effects of Ezh2 ^Y641F mutations at various stages of development, with a focus on the hematopoietic system. We found that ubiquitous heterozygous Ezh2 ^Y641F expression at birth, or conditional expression in hematopoietic or mesenchymal stem cells, led to decreased survival due to hematopoietic defects and bone marrow failure, with no evidence of malignancy. In contrast, Ezh2 ^Y641F expression in committed B

SUBMITTER: Zimmerman SM 

PROVIDER: S-EPMC11601384 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature