A multi-institutional academic and industry research team led by investigators from Massachusetts General Hospital (MGH) and the Harvard Stem Cell Institute has identified a promising new approach to the treatment of acute myeloid leukemia (AML). In their report, published in the September 22, 2016 issue of Cell, the investigators identify a crucial dysfunction in blood cell development that underlies AML and show that inhibiting the action of a specific enzyme prompts the differentiation of leukemic cells, reducing their number and decreasing their ability to propagate the cancer. The Cell article is titled “Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia.” "AML is a devastating form of cancer; the five-year survival rate is only 30 percent, and it is even worse for the older patients who have a higher risk of developing the disease," says David Scadden, M.D., Director of the MGH Center for Regenerative Medicine (MGH-CRM), Co-Director of the Harvard Stem Cell Institute (HSCI), and senior author of the Cell paper. "New therapies for AML are extremely limited -- we are still using the protocols developed back in the 1970s -- so we desperately need to find new treatments." In AML, the normal process by which myeloid stem cells differentiate into a specific group of mature white blood cells is halted, leading to the proliferation of immature, abnormal cells that crowd out and suppress the development of normal blood cells. A wide range of genetic changes occurs in AML, but the authors proposed that the effects on differentiation had to funnel through a few shared molecular events.
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