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Innovative Anti-Leukemia Strategy

Innovative Anti-Leukemia Strategy

Acute myeloid leukemia (AML) is a devastating and hard-to-treat cancer of the blood and bone marrow. Defects in the transcription factor PU.1 are known to play a role in causing AML. But until now, all efforts at targeting AML caused by defective PU.1 have failed. Transcription factors—proteins that regulate gene expression by binding to DNA—have historically been very hard to target with drugs. Ulrich G. Steidl, M.D., Ph.D., and colleagues reported last October in the Journal of Clinical Investigation that they had inhibited PU.1 through the novel strategy of targeting the minor groove—a part of the DNA double helix to which transcription factors don’t usually bind. The researchers’ first-in-class PU.1 inhibitors successfully halted overactive cell division in blood samples from AML patients, suggesting that targeting PU.1 could be a successful strategy for treating the disease. Dr. Steidl is the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research, director of the Stem Cell Isolation and Xenotransplantation Facility and a professor of cell biology and of medicine at Einstein and associate chair for translational research in oncology at Montefiore.

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