STAT5B leukemic mutations, altering SH2 tyrosine 665, have opposing impacts on immune gene programs.

ABSTRACT: STAT5B is a vital transcription factor for lymphocytes. Here, function of two STAT5B mutations from human T cell leukemias: one substituting tyrosine 665 with phenylalanine (STAT5B^Y665F), the other with histidine (STAT5B^Y665H) was interrogated. In silico modeling predicted divergent energetic effects on homodimerization with a range of pathogenicity. In primary T cells in vitro STAT5B^Y665F showed gain-of-function while STAT5B^Y665H demonstrated loss-of-function. Introducing the mutation into the mouse genome illustrated that the gain-of-function Stat5b ^Y665F mutation resulted in accumulation of CD8⁺ effector and memory and CD4⁺ regulatory T-cells, altering CD8⁺/CD4⁺ ratios

SUBMITTER: Lee HK 

PROVIDER: S-EPMC11722272 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature