Acute Myeloid Leukemia Stem Cells-Updates and Controversies

Acute myeloid leukemia (AML) is a genetically heterogeneous disorder of the hematopoietic system marked by maturation arrest and proliferation of leukemic cells in the bone marrow. Although most patients can be induced into a remission with initial chemotherapy, the majority is destined to relapse, with most relapsed patients eventually succumbing to their disease. The reservoir for relapse has been postulated to be a pool of "leukemic stem cells" (LSC), which have the capability to self-renew, giving rise to both new LSCs and non-self renewing progeny to recapitulate the full phenotypic and functional diversity of the primary leukemia. It is thought that LSCs resist chemotherapy by multiple mechanisms including increased quiescence, the expression of multi-drug resistance pumps, and residence in a protective bone marrow (BM) microenvironment. To date, direct evidence that LSCs represent the chemo-resistant population in AML is limited, and much work remains to more fully characterize this largely conceptual cell type in the pathogenesis of treatment resistance and disease relapse.