Dr. Melnick Reveals Genetic Pathway in AML
December 3, 2010
Acute myelogenous leukemia (AML), with more than 12,000 new diagnoses each year, is a particularly stealthy cancer. But a team of researchers led by Ari M. Melnick, MD, Associate Professor of Medicine at Weill Cornell Medical College, have caught it in the act. In research published this week in the online issue of Cancer Cell, Dr. Melnick and his colleagues elucidate how a mutation in the genes that produce the metabolic enzymes IDH1 and IDH2 leads directly to the transformation of a healthy bone marrow cell to a cancerous one — findings that may result in new drugs for AML, one of the most common types of adult leukemia.
The breakthrough comes fast on the heels of Dr. Melnick's recent success with laboratory tests of a new combinatorial therapy for diffuse large B cell lymphoma, also published this month.
In their nonmutated form, IDH1 and IDH2 code for enzymes that play a central role in the production of cellular energy. As Dr. Melnick's team describes, the mutation in question — present in a subset of AML patients — triggers the overactivity of a particular epigenetic "switch" that causes other genes to function abnormally. Compounding this effect, the mutated IDH1/2 also generate an acid that inhibits a protective factor called TET2, which in normal cells works to counteract the out-of-control epigenetic activity. The research provides a specific molecular target at which investigators can aim the development of new drug treatments. And the findings go further than just this subset of AML patients — IDH1 is also frequently mutated in malignant brain tumors.
Funded by the Leukemia and Lymphoma Society, the collaborative effort led by Dr. Melnick involved the participation of numerous laboratories, across the country and in Europe, as well as the pharmaceutical industry. Dr. Melnick is Director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell.
Click here to read the Cancer Cell paper.
Click here to read the WCMC press release.