High activation of STAT5A drives peripheral T-cell lymphoma and leukemia.

ABSTRACT: Recurrent gain-of-function mutations in the transcription factors STAT5A and much more in STAT5B were found in hematopoietic malignancies with the highest proportion in mature T- and natural killer-cell neoplasms (peripheral T-cell lymphoma, PTCL). No targeted therapy exists for these heterogeneous and often aggressive diseases. Given the shortage of models for PTCL, we mimicked graded STAT5A or STAT5B activity by expressing hyperactive Stat5a or STAT5B variants at low or high levels in the hematopoietic system of transgenic mice. Only mice with high activity levels developed a lethal disease resembling human PTCL. Neoplasia displayed massive expansion of CD8⁺ T cells and destructive organ infiltration. T cells were cytokine-hypersensitive with activa

SUBMITTER: Maurer B 

PROVIDER: S-EPMC7012494 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature