Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

Abstract

Accumulating evidence support the notion that acute myeloid leukemia (AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells (LSC). Similar to their normal counterpart, hematopoietic stem cells (HSC), LSC possess self-renewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normal HSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC.

Keywords: Acute myeloid leukemia, Leukemia stem cell, Immunotherapy, Cancer stem cell, Cell therapy

Core tip: Acute Myeloid Leukemia (AML) remains an incurable disease in most of cases. Leukemia stem cells (LSC) are a subpopulation of leukemic cells responsible for the continued proliferation and propagation of bulk leukemic cells. Growing evidence support the notion that LSCs are the root source of disease relapse and treatment resistance. Here we review the literature on historical overview of the discovery of LSC, identification and separation of LSC and strategies of targeting LSC as a potential cure for AML.