New treatment options are badly needed for acute myeloid leukemia (AML), a relatively rare form of cancer. The malignancy begins in the bone marrow, and from there, can spread rapidly to the bloodstream, depriving the body of the essential blood cells that carry oxygen and fight infections. Now, new work from a team led by Rockefeller University researchers in New York City has revealed a potential genetic weakness of this leukemia, offering insights into the molecular mechanisms behind AML, and suggesting a new target for drug development. Previously, researchers had identified a variety of mutations associated with this disease, including a DNA rearrangement found in approximately 15 percent of patients. The abnormal DNA-binding protein produced as a result of this rearrangement takes on entirely new functions, dramatically altering a set of genes that are turned on in a cell to promote the cancer. But how this mutation effects these changes has remained a mystery. In their new work published in the October 15, 2015 issue of Genes and Development, the researchers describe how they identified the molecular mechanism responsible for this gene activation. Their article is titled “JMJD1C Is Required for the Survival of Acute Myeloid Leukemia by Functioning As a Coactivator for Key Transcription Factors.” The research team, led by Dr. Robert G. Roeder, Arnold and Mabel Beckman Professor and Head of Rockefeller's Laboratory of Biochemistry and Molecular Biology, began by searching for proteins that interact with the mutant protein, known as AE (AML/ETO) fusion protein, which is produced by the DNA rearrangement. Their screen identified JMJD1C, an enzyme that removes chemical tags, known as methyl groups, from histones, which are proteins contained in chromosomes.
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