Abstract
Most patients with acute myeloid leukemia treated with chemotherapy relapse. It is increasingly recognized that the cause of chemoresistance and relapse resides within the leukemia stem cell population. Successful eradication of leukemia stem cells would require a comprehensive profile of both the acquired molecular lesions and intrinsic features of leukemia stem cells. This review describes recent work identifying molecular markers that may lead to development of novel therapeutics, ultimately aiming to eradicate leukemia stem cells in acute myeloid leukemia. In recent years, novel specific cell surface antigens have allowed identification of leukemia stem cells and permitted their distinction from normal hematopoietic stem cells. Novel concepts of leukemia stem cells and niche interaction have elucidated the mechanisms that control leukemia stem cell survival and chemoresistance. Recent detection of genetic aberrations affecting regulators of HOX gene expression and chromatin modifying enzymes, such as CDX2 and hDOT1L, respectively, elucidates new key players in stem cell self-renewal and leukemic transformation. The discovery of novel markers and survival pathways for leukemia stem cells has increased our potential to specifically target and eliminate the leukemic stem cell compartment, which is likely to improve clinical outcomes in acute myeloid leukemia.
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