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When leukemia returns, gene that mediates response to key drug often mutated
Date:3/9/2011

(MEMPHIS, Tenn. March 9, 2011) Despite dramatically improved survival rates for childhood acute lymphoblastic leukemia (ALL), relapse remains a leading cause of death from the disease. Work led by St. Jude Children's Research Hospital investigators identified mutations in a gene named CREBBP that may help the cancer resist steroid treatment and fuel ALL's return.

CREBBP plays an important role in normal blood cell development, helping to switch other genes on and off. In this study, researchers found that 18.3 percent of the 71 relapsed-ALL patients carried alterations in the DNA sequence of CREBBP. In contrast, the gene's sequence was changed in just one of the 270 young leukemia patients whose cancer did not return.

Investigators say the gene is a potential indicator of relapse risk because of the high frequency of CREBBP mutations in relapsed patients and evidence the changes persisted from diagnosis or emerged at relapse from subpopulations of leukemia cells present from the beginning. Researchers also found evidence the changes occur in important regulatory regions of the gene and affect cell function, including how cancer cells respond to the steroids that play an important role in cancer treatment. The work appears in the March 10 issue of the scientific journal Nature.

"This study gives us further evidence that detailed genomic studies can identify important mutations that influence tumor response to treatment," said Charles Mullighan, M.D., Ph.D., assistant member of the St. Jude Department of Pathology. Mullighan and Jinghui Zhang, Ph.D., an associate member of the St. Jude Department of Computational Biology, are co-first authors. Mullighan is also the corresponding and senior author.

In the same issue of Nature, investigators also reported that deletions and deactivating mutations in CREBBP and a related gene known as EP300 occurred in about one-third of patients identified with one of the two mos
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Contact: Carrie Strehlau
carrie.strehlau@stjude.org
901-595-2295
St. Jude Children's Research Hospital
Source:Eurekalert

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