New research indicates that drugs that target a cell growth pathway known as the JAK-STAT pathway are likely to be effective against certain chronic leukemias.

Researchers recently discovered that a mutation in the JAK2 gene is responsible for the majority of cases of three rare kinds of chronic leukemia, all of which are resistant to the leukemia drug Gleevec. The new study identifies a second mutation in the same pathway that can also cause the disease, leading researchers to think that drugs targeting JAK-STAT signaling should be effective against leukemias caused by either mutation.

In a study published July 18, 2006, in the online journal Public Library of Science Medicine, a team led by Yana Pikman, a Howard Hughes Medical Institute (HHMI) medical research fellow, and Ross L. Levine, a former HHMI medical research fellow, found a mutation in a gene called MPL in a subset of leukemias that lacked the more common JAK2 mutation. HHMI medical research fellows are medical students who compete for the opportunity to spend a year doing full-time research.

D. Gary Gilliland, an HHMI investigator at Brigham and Women's Hospital and Harvard Medical School, is co-author of the paper.

"We're excited about this finding because we hope to identify a common drug, an inhibitor of the JAK2 pathway, to treat patients with these types of leukemia," said Gilliland, who in 2005 worked with Levine to identify the JAK2 mutation responsible for most cases of myelofibrosis (MF), polycythemia vera (PV), and essential thrombocytosis (ET).

JAK2 normally encodes a protein that helps control the production of new blood cells. But when the gene is mutated, JAK2's growth-stimulating signal gets turned on permanently, causing overproduction of one or another type of blood cell. In different forms of the disease, the overabundant cells may be various kinds of white blood cells, platelets, or oxygen-carrying red blood cells.

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Contact: Jennifer Donovan
donovanj@hhmi.org
301-215-8859
Howard Hughes Medical Institute
17-Jul-2006