Targeting Leukemia Stem Cells: Which Pathways Drive Self-Renewal Activity in T-Cell Acute Lymphoblastic Leukemia?

T-Cell acute lymphoblastic leukemia (T-ALL) is a malignancy of white blood cells, characterized by an uncontrolled accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and crowd into the bone marrow, preventing it from making normal blood cells and spilling out into the bloodstream. Recent studies suggest that only discrete cell populations that possess the ability to recreate the entire tumour might be responsible for the initiation and propagation of T-ALL. Those unique cells are commonly called “cancer stem cells” or, in the case of hematopoietic malignancies, “leukemia stem cells” (LSCs). Like normal hematopoietic stem cells, LSCs are thought to be capable of self-renewal, during which, by asymmetrical division, they give rise to an identical copy of themselves as well as to a daughter cell that is no longer capable of self-renewal activity and represents a more “differentiated” progeny. Here, we review the main pathways of self-renewal activity in LSCs, focusing on their involvement in the maintenance and development of T-ALL. New stem cell–directed therapies and LSC-targeted agents are also discussed.