Regulation of PHLPP2 Expression in AML

Abstract

The phosphatase PHLPP2 functions as a tumor suppressor by activating the proapoptotic function of Bcl-2 protein Noxa in leukemia cells. PHLPP2 is downregulated or depleted in specific acute myeloid leukemia (AML) subtypes. We hypothesize that AML has evolved mechanisms to suppress PHLPP2 expression and/or phosphatase activity. We measured the expression of PHLPP2 in a small panel of leukemia cell lines. PHLPP2 transcript was found in the lines despite the lack of protein expression. To test the hypothesis that PHLPP2 translation is blocked in AML cell lines, we assayed levels of miR-17-92, a miRNA cluster which targets PHLPP2. Levels of miR-17-92 were increased in AML versus acute lymphoid leukemia (ALL) lines. Furthermore, PHLPP2 protein was less stable in an M5 AML line compared to ALL. These studies offer insights into novel protein suppression mechanisms and lay the foundation for further investigations into PHLPP2 as a biomarker and therapeutic target for AML.