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news.Scientists at the University of North Carolina at Chapel Hill have identified an enzyme that helps trigger the development of leukemia, offering a potential target for new drugs.
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Researchers found that the enzyme, hDOT1L, activates a set of genes that play a key role in acute myeloid leukemia (AML), a rare form of leukemia. The new findings, which appear in the journal Cell, demonstrate that hDOT1L helps transform, or immortalize, bone marrow cells, causing their unrestrained growth, a hallmark of leukemia.
“We demonstrate that not only is hDOT1L required for transformation of bone marrow cells, but, more importantly, that its enzymatic activity is required to maintain the transformed status,” said Dr Yi Zhang, associate professor of biochemistry and biophysics at UNC’s School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. “That means if we have a way to prevent the activity of hDOT1L, then the affected cells of particular leukemia patients can be killed.”
Zhang’s study reveals that leukemia cells containing the fusion protein MLL-AF10 require hDOT1L to survive. When the researchers introduced into leukemia cells a defective form of hDOT1L, one that cannot methylate histone proteins, the cells were no longer able to grow. This, the researchers claim, suggests the potential of hDOT1L as a possible drug target.