The role of the tumor suppressor PTEN in Chronic Myeloid Leukemia pathogenesis

The Phosphatase and Tensin homolog detected on chromosome Ten PTEN displays tumor suppressive functions within two different cellular compartments. In the cytoplasm/membrane, it controls cellular proliferation, survival and metabolisms, through the de-phosphorylation of the phosphatidylinositol (3,4,5) triphosphate (PIP3), therefore counteracting the PI3K-AKT pathway. In the nucleus, it regulates proliferation and genomic stability through phosphatase independent mechanisms. Chronic Myeloid Leukemia is a myeloproliferative disorder generated by the translocation t(9;22), which encodes for the chimeric protein BCR-ABL. PTEN was shown to play an essential role in CML pathogenesis in a murine model. We and others have demonstrated that PTEN is affected in human CML though non genomic loss of function mechanisms. Furthermore, we proposed strategies to reactivate PTEN in CML cells, with relevant therapeutic implications.