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Gene sequencing project identifies abnormal gene that launches rare childhood leukemia
Date:11/12/2012

Research led by the St. Jude Children's Research Hospital Washington University Pediatric Cancer Genome Project has identified a fusion gene responsible for almost 30 percent of a rare subtype of childhood leukemia with an extremely poor prognosis.

The finding offers the first evidence of a mistake that gives rise to a significant percentage of acute megakaryoblastic leukemia (AMKL) cases in children. AMKL accounts for about 10 percent of pediatric acute myeloid leukemia (AML). The discovery paves the way for desperately needed treatment advances.

Investigators traced the genetic misstep to the rearrangement of chromosome 16, which brings together pieces of two genes and sets the stage for production of an abnormal protein. The fusion protein features the front end of CBFA2T3, a blood protein, and the back of GLIS2, a protein that is normally produced only in the kidney. Work that appears in the November 13 edition of the journal Cancer Cell reports that in a variety of laboratory models the CBFA2T3-GLIS2 protein switched on genes that drive immature blood cells to keep dividing long after normal cells had died. This alteration directly contributes to leukemia.

AMKL patients with the fusion gene were also found to be at high risk of failing therapy. Researchers checked long-term survival of 40 AMKL patients treated at multiple medical centers around the world and found about 28 percent of patients with the fusion gene became long-term survivors, compared to 42 percent for patients without CBFA2T3-GLIS2. Overall long-term survival for pediatric AML patients in the U.S. is now 71 percent.

"The discovery of the CBFA2T3-GLIS2 fusion gene in a subset of patients with AMKL paves the way for improved diagnostic testing, better risk stratification to help guide treatment and more effective therapeutic interventions for this aggressive childhood cancer," said James Downing, M.D., St. Jude scientific director and the paper's c
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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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