Delineating the distinct role of AKT in mediating cell survival and proliferation induced by CD154 and IL-4/IL-21 in chronic lymphocytic leukemia.

ABSTRACT: The functional significance of AKT in chronic lymphocytic leukemia (CLL) remains unclear. Given the importance of non-malignant T cells in regulating clonal expansion in CLL, we investigated the role of AKT in T cell-mediated cytoprotection and proliferation using an established co-culture system in which primary CLL cells were incubated on a monolayer of transfected mouse fibroblasts expressing human CD40L (CD154). Stimulation of CLL cells via CD40 induced activation of AKT, which was closely associated with downregulation of its negative regulator PTEN, and protected CLL cells from killing by bendamustine. This cytoprotective effect of CD40 stimulation was prevented by a selective inhibitor of AKT. Stimulation of CLL cells with CD154 + IL-4 or IL-21 induced proliferation detected as redu

SUBMITTER: Chapman EA 

PROVIDER: S-EPMC5732702 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature