Developmental stage and cellular context determine oncogenic and molecular outcomes of <i>Ezh2</i> ^Y641F mutation in hematopoiesis.

ABSTRACT: Mutations in the histone methyltransferase enhancer of zeste homolog 2 (EZH2), particularly the neomorphic Y641F hot spot mutation, are implicated in hematologic malignancies. However, how developmental timing and cellular context influence their oncogenic potential remains poorly understood. Here, we used a conditional Ezh2 ^Y641F allele with multiple tissue-specific Cre drivers to investigate the effects of these mutations across hematopoietic development. We found that ubiquitous or early expression of Ezh2 ^Y641F led to bone marrow failure and reduced survival with no evidence of transformation. In contrast, expression in committed B cells using CD19-Cre consistently induced B-cell lymphomas, underscoring a context- and stage-specific requirement for t

SUBMITTER: Zimmerman SM 

PROVIDER: S-EPMC12356278 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature