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.