Acute myeloid leukemia (AML) is an aggressive malignancy of immature myeloid cells in the bone marrow affecting almost 20,000 adults annually in the US, most of them over the age of 65. Current standard of care includes treatment with high dose chemotherapy and often includes allogeneic hematopoietic cell transplantation. Even with these aggressive treatments, five-year overall survival is between 25-30%, and much lower for those over age 65. Normal blood development is organized as a cellular hierarchy initiated and maintained by self-renewing hematopoietic stem cells (HSC). Similarly, AML is also organized as a cellular hierarchy, with a subset of aberrant leukemia stem cells (LSC) driving the disease (Figure 1). Recent studies have demonstrated that AML LSC are not always rare or restricted to immunophenotypically defined populations. The clinical significance of the AML LSC model is supported by the demonstration that LSC gene expression signatures are prognostic in multiple cohorts of patients. Clinically, this model implies that LSC must be eradicated in order to achieve cures. Currently, patients treated with standard chemotherapy exhibit clinical responses, including complete remissions in most cases. However, the majority of patients relapse, presumably due to incomplete elimination of LSC. Thus, novel therapies must be developed that target and eliminate LSC in order to cure AML.
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