Differentiation Therapy of Acute Myeloid Leukemia
Abstract: Acute myeloid leukemia (AML) is characterized by a differentiation block in the myeloid lineages of the hematopoiesis. After the success of the all-trans retinoic acid (ATRA) differentiation therapy which overcomes this differentiation block for AML subtype acute promyelocytic leukemia, attempts have been made to find similar therapies for the remaining subtypes. Differentiation therapy candidate H4 (derived from a library of small natural products) has been shown to induce phenotypic differentiation in both an AML cell line and a primary AML sample. In this study, we show that treatment with H4 increases the sensitivity to IL3, which is a differentiation-promoting cytokine in normal hematopoiesis, by upregulating expression of its receptor. This knowledge can be used to design future differentiation therapies for AML.
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