Prognostic and Therapeutic Significance of Stem Cell Heterogeneity in AML
AML is a blood cancer from which most patients will eventually die despite aggressive therapy. It is thought that only a minute population of cancer cells ("leukemia stem cells" or LSCs) causes/maintains the leukemia. Thus, there is great interest in understanding LSCs to develop novel treatments that specifically destroy these cells. LSCs may be diverse across patients: in some, they may resemble a normal blood stem cell whereas in others, they may look like a maturing white blood cell. We believe that this diversity is important for response to treatment and likelihood of cure but LSCs are poorly characterized so far because they could not be grown in the laboratory. We have now developed a novel system to grow and study cells from AML patients, including LSCs. We plan to use this method to study a large number of patient specimens to better understand LSCs and how genetic changes accumulate in them. These studies are aimed at improving our understanding of how LSCs are connected to therapeutic response and prognosis. By doing so, our studies may provide the rationale for a conceptually novel classification of human AML that improves our accuracy of predicting outcome of therapy. They may also discover novel targets for stem cell-directed therapies and identify appropriate subsets of patients in whom such therapies should be tested and utilized. Together, our studies may improve and individualize our efforts to eliminate stem cells in human AML and, ultimately, lead to a better chance of cure for patients with AML.