CD82 Regulates STAT5/IL-10 and Supports Survival of Acute Myelogenous Leukemia Cells.

Abstract 2981

We recently reported that adhesion molecule CD82 is aberrantly expressed in CD34⁺/CD38⁻ leukemia stem cells (LSCs) (ASH 2010; Abstract 2168.). Here, we report the results of a functional analysis of CD82 in CD34⁺/CD38⁻ acute myelogenous leukemia (AML) cells. Short hairpin (sh)RNA-mediated downregulation of CD82 resulted in dephosphorylation of STAT5 and a decrease in the level of IL-10. In contrast, forced expression of CD82 in CD34⁺/CD38⁺ AML cells by transduction with CD82-expressing lentiviral particles resulted in an increase in the levels of p-STAT5 and IL-10. Chromatin immunoprecipitation (ChIP) assay results indicated that STAT5A binds to the promoter region of the IL-10 gene, while reporter gene assay results indicated stimulation of IL-10 expression at the transcriptional level. These results suggest that CD82 positively regulates the STAT5/IL-10 signaling pathway. Notably, exposure of CD34⁺/CD38⁻ AML cells to IL-10 stimulated clonogenic growth of these cells. Moreover, shRNA-mediated downregulation of CD82 expression in CD34⁺/CD38⁻ AML cells impaired AML reconstitution in immunodeficient mice in parallel with downregulation of STAT5. Taken together, our data suggest that the CD82/STAT5/IL-10 signaling pathway is involved in the survival of CD34⁺/CD38⁻ AML cells and may thus be a promising therapeutic target for eradication of AML LSCs.