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New clue in leukemia mystery: Researchers identify 'poison' employed by deadly enzyme mutations
Date:12/3/2010

NEW YORK (Dec. 2, 2010) -- There is new hope for people with acute myelogenous leukemia (AML), a fast-growing cancer of the blood and bone marrow. Research led by Weill Cornell Medical College and published today in the online edition of the journal Cancer Cell reveals a surprising and unexpected cancer-causing mechanism. The investigators discovered that newly identified mutant enzymes in AML create a chemical poison to cause leukemia. Their findings should prove useful in treating patients by providing a molecular target against which to develop new drugs against one subset of AML as well as other cancers.

AML is one of the most common types of leukemia among adults, with an estimated 12,300 new cases diagnosed in the United States each year and 8,950 deaths, according to the American Cancer Society. People with AML have abnormal cells inside their bone marrow that quickly multiply, replacing healthy blood cells in the bone marrow and leading to infections, bleeding and severe anemia.

The large-scale, international, collaborative research effort scrutinized the genomes of 750 AML patients from the United States and Europe for chemical clues to better understand how leukemia arises from normal bone marrow cells. Using computational tools to sift through millions of data points, they discovered a unique chemical signature in the genomes of patients with mutations in either of two enzymes called IDH1 and IDH2, which occur frequently in AML.

Dr. Ari Melnick of Weill Cornell Medical College and his principal co-authors -- including Dr. Craig B. Thompson, president of Memorial Sloan-Kettering Cancer Center (MSKCC), and Dr. Ross L. Levine, also of MSKCC -- discovered this chemical signature: a massive accumulation of DNA methylation that causes genes to function abnormally, leading to AML. They went on to show that IDH1 and IDH2 mutations generate a "poison" that blocks the ability of a protective factor called TET2 to remove the me
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Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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