PTEN and leukemia stem cells

Leukemia stem cells (LSCs) are considered responsible for leukemia initiation, relapse and resistance to chemotherapy. These cells have self-renewal capacity and originate the other cells in the leukemia pool. Therefore, in order to completely eradicate leukemia cells and consequently cure the disease, therapies should in principle necessarily target LSCs. However, the fact that LSCs share functional and phenotypic properties with normal hematopoietic stem cells (HSCs) poses a significant challenge: how to target LSCs without damaging normal HSCs and compromising hematopoiesis? The discovery that PTEN regulates LSCs and HSCs through different mechanisms, demonstrated that it is possible to identify pathways that differentially impact leukemia and normal stem cell function and opened new therapeutic perspectives for the selective elimination of LSCs. In this review, we briefly discuss the mechanisms that regulate PTEN function in LSCs and HSCs and their potential for the development of LSC-targeted therapies.