Trio of leukemias share a single mutation

Three leukemias that affect as many as 100,000 people in the United States are all caused by acquired mutations that alter a specific enzyme controlling blood cell proliferation, according to new studies by Howard Hughes Medical Institute (HHMI) researchers.

Identifying the genetic malfunction that causes these disorders raises the hope that researchers may be able to devise a targeted therapy, just as they have done for chronic myelogenous leukemia (CML), which is presently treated with Gleevec. The three leukemias that share a common genetic cause are polycythemia vera (PV), essential thrombocythemia (ET) and myeloid metaplasia with myelofibrosis (MMM).

The research team, which was led by Gary Gilliland, an HHMI investigator at Brigham and Women's Hospital and Harvard Medical School, published its findings on March 24, 2005, in an immediate early publication in the journal Cancer Cell. Gilliland and Stephanie Lee of the Dana-Farber Cancer Institute, and co-first authors Ross Levine and Martha Wadleigh, collaborated with researchers from the University of Leuven - Flanders Interuniversity Institute for Biotechnology in Belgium, University Hospital of Ulm in Germany, the Broad Institute, and the Mayo Clinic.

According to Gilliland, the researchers analyzed the blood of patients with the three leukemias for a defect that permanently activated a particular type of enzyme called a tyrosine kinase. Tyrosine kinases are cellular switches that control an array of cellular processes. The researchers concentrated on the enzymes because activated tyrosine kinases had been shown to cause other similar myeloproliferative diseases such as CML, he said. Also, in earlier work, Gilliland and his colleagues had isolated the mutated gene that produces the activated tyrosine kinase responsible for the myeloproliferative disease hypereosinophilic syndrome.

"The three disorders that we studied were the last of these diseases whose causes had not yet been discovered,

Contact: Jim Keeley
Howard Hughes Medical Institute

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