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Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a malignant disease characterized by a disruption in normal hematopoietic differentiation and the accumulation of abnormal, immature myeloid cells in the bone marrow and peripheral blood. Current disease management strategies rely on cytogenetic profiling to classify AML disease states into various prognostic categories. For example, recurrent chromosomal rearrangements involving the mixed lineage leukemia (MLL) gene are commonly observed, and the resulting novel fusion proteins, such as MLL-AF9, are associated with poor outcomes.

Recent advances in molecular genetics have identified additional markers that may be useful for diagnosing AML, identifying leukemic stem cells, and developing targeted therapeutics. Increased expression of cell surface markers such as TIM-3, IL-3 R alpha (CD123), and CD44 can be used to distinguish normal CD34+CD38- hematopoietic stem cells and the subpopulation of leukemic stem cells. In addition, monoclonal antibodies targeted against leukemic stem cell surface antigens such as CD44, CD47, and IL-3 R alpha, have demonstrated efficacy in the treatment of AML in animal models.