Akt: A double-edged sword for hematopoietic stem cells

The phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway is dysregulated in a wide range of malignancies, including leukemia, and several members of this pathway are attractive therapeutic targets in oncology1. Although Akt is constitutively phosphorylated in up to 90% of cases of acute myeloid leukemia (AML), its role in AML has been unclear2. In some cases, Akt activation is attributed to activation of tyrosine kinases, such as BCR-ABL or FLT3-ITD, but in many cases the mechanism of Akt phosphorylation and its significance is unknown. Is AKT activation simply a marker of leukemic transformation, or is it a driver of leukemogenesis?