Partial trisomy 21 contributes to T-cell malignancies induced by JAK3-activating mutations in murine models.

ABSTRACT: JAK3-activating mutations are commonly seen in chronic or acute hematologic malignancies affecting the myeloid, megakaryocytic, lymphoid, and natural killer (NK) cell compartment. Overexpression models of mutant JAK3 or pharmacologic inhibition of its kinase activity have highlighted the role that these constitutively activated mutants play in the T-cell, NK cell, and megakaryocytic lineages, but to date, the functional impact of JAK3 mutations at an endogenous level remains unknown. Here, we report a JAK3^A572V knockin mouse model and demonstrate that activated JAK3 leads to a progressive and dose-dependent expansion of CD8⁺ T cells in the periphery before colonization of the bone marrow. This phenotype is dependent on the γc chain of cytokine receptors and presents s

SUBMITTER: Rivera-Munoz P 

PROVIDER: S-EPMC6039658 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature