Pathways involved in the evolution of leukemic stem cells.

Understanding the evolution of the cancer cell from a normal cell holds the key to developing novel, potent therapies against cancer. Two hypotheses describing the origins of cancer cells have been developed: one stating that any normal cell can acquire the ability to replicate indefinitely and evade natural cell death signals by accumulating multiple mutations over time, and a second suggesting that adult stem cells, by virtue of their pre-existing capacity for differentiation, asymmetric division and self-renewal, are the more likely targets of carcinogenic mutation. The leukemic stem cell (LSC) was the first cancer stem cell described. Evolving from the aberrant regulation and mutation of hematopoietic stem cells (HSCs), LSCs are suggested to encompass the subset of tumor cells sufficient for continued tumorigenesis. LSCs were also found to differentiate into a variety of cancer cell progenitors in a manner reminiscent of HSC differentiation, also explaining the observed heterogeneity of leukemic cells. How these cells form from HSCs remains to be fully comprehended. However, over recent years, marked progress has been made in contributing to our knowledge of cancer stem cells and what signaling cascades are involved in their development. Therapeutics targeting the pathways allowing for LSCs to sustain proliferation and self-renewal may prove to be more effective treatments for lymphoblastic leukemia.