Identification and characterization of leukemia stem cells in T-cell acute lymphoblastic leukemia (T-ALL)

The traditional view of cancer is that tumours are composed of identical cells, and thus the goal of treatment is to kill every one of those cancer cells in the body. In a tumour, it is estimated that a very small fraction of cells (perhaps 1 in 10,000) are ""cancer stem cells"", which are the cells that have the capacity to self-renew or to create progeny that carry the same properties as the parent cell. A new cancer treatment theory hypothesizes that to treat cancer, the only cells that need to be killed off are these cancer stem cells, and once they are gone the rest of the tumour should regress on its own. The challenge becomes to first identify the cancer stem cells and then design a drug that would specifically kill those cancer stem cells only. Dr. Vincenzo Giambra's lab has recently shown that cancer stem cells exist in a particular type of blood cancer called T-cell acute lymphoblastic leukemia (T-ALL). Although T-ALL is not a common form of cancer, it is unique in that more than 50 per cent of cases carry mutations that inappropriately activate a gene called Notch1, which plays an important role in normal stem cell maintenance. Dr. Giambra's research objectives are to identify how cancer stem cells are able to evade the immune system and thrive in T-ALL, and to design a drug that specifically kills those cancer stem cells. He will be isolating cancer stem cells from a unique mouse model that has Notch1-induced T-ALL, using specific molecules on the surface of cancer stem cells. He will also compare leukemias generated from mice of different ages to see if they express different genes, with the goal of using this information to design new drugs that may help to cure more patients with leukemia. These studies will allow Dr. Giambra to define the genetic programs and pathways that are responsible for conferring self-renewal upon the leukemia stem cells; they will also provide rationale for the design of new therapies that specifically target the stem cells. In focusing his efforts toward killing only the cancer stem cells, Dr. Giambra expects these therapies will be more effective for achieving a cure and less toxic to the patient. Finally, he anticipates that some of the genetic programs and pathways he will identify will be critical for self-renewal of Notch T-ALL stem cells and may be important for self-renewal of all cancer stem cells in general. Thus, these results may prove useful to investigators studying other cancers as well.