Structural and functional consequences of the STAT5B^N642H driver mutation.

ABSTRACT: Hyper-activated STAT5B variants are high value oncology targets for pharmacologic intervention. STAT5B^N642H, a frequently-occurring oncogenic driver mutation, promotes aggressive T-cell leukemia/lymphoma in patient carriers, although the molecular origins remain unclear. Herein, we emphasize the aggressive nature of STAT5B^N642H in driving T-cell neoplasia upon hematopoietic expression in transgenic mice, revealing evidence of multiple T-cell subset organ infiltration. Notably, we demonstrate STAT5B^N642H-driven transformation of γδ T-cells in in vivo syngeneic transplant models, comparable to STAT5B^N642H patient γδ T-cell entities. Importantly, we present human STAT5B and STAT5B^N642H crystal structures, which propose alternative mutatio

SUBMITTER: de Araujo ED 

PROVIDER: S-EPMC6555848 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature