Stem Cells and Leukemia

In the last few years, the concepts governing our understanding of cancer have changed. In particular, the point of view that many leukemias are developmentally well-defined and, like in normal hematopoiesis, driven by a relatively small subset of cells called leukemia stem cells (LSCs) has become well-established. Recent studies suggest that defined subsets of LSCs within a tumor are capable of recreating the entire tumor and thus are responsible for relapse/recurrence and metastasis. This subset of “cancer stem cells” has been postulated to possess certain properties akin to those characterized in hematopoietic stem cells such as the capacity to (1) self-renew and to (2) give rise to non-self-renewing or “differentiated” progeny cells that make up the bulk of a tumor. Among the hematopoietic malignancies, acute myeloid leukemia (AML) is the best characterized thus far with respect to “leukemia stem cells” and much data support that the above two properties exist within a relatively rare subpopulation. Related ­studies have also demonstrated that leukemia stem cells are functionally distinct from bulk cells. These subsets are relatively quiescent or slowly cycling, whereas clonogenic progenitors (“differentiated” progeny which cannot self-renew) proliferate rapidly. Current antiproliferative chemotherapy usually affects these dividing progenitors and induces disease relapses as defined by decreased bulk tumor burden. Relapse is not uncommon however, suggesting the quiescent leukemia stem cells are not effectively removed from circulation by existing therapies. Therefore, new therapies that specifically target leukemia stem cells hold great promise for achieving the elusive cure for cancer.