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Inherited DNA change explains overactive leukemia gene
Date:5/25/2012

  • An overactive BAALC gene in acute leukemia cells identifies patients whose disease is likely to respond poorly to standard therapy.
  • This study discovered why the gene is often overactive.
  • The findings may provide a prognostic marker that can help guide therapy in these patients.

COLUMBUS, Ohio A small inherited change in DNA is largely responsible for overactivating a gene linked to poor treatment response in people with acute leukemia.

The study by researchers at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James) focused on a gene called BAALC. This gene is often overactive, or overexpressed, in people with acute myeloid or acute lymphoblastic leukemia, and it indicates that the disease is likely to respond poorly to standard therapy.

This study discovered that BAALC overexpression is caused by a small change called a single nucleotide polymorphism, or SNP (pronounced "snip") in the gene's DNA. The SNP alters the gene's "On" switch, allowing a different molecule to keep it "running" when it shouldn't.

"We want to emphasize," says principal investigator Dr. Albert de la Chapelle, professor of medicine, the Leonard J. Immke Jr. and Charlotte L. Immke Chair in Cancer Research, and co-leader of the Molecular Biology and Cancer Genetics Program, "that this SNP does not raise an individual's risk of developing leukemia, but it does predispose to overexpression of the BAALC gene, which is associated with leukemia development and poor response to treatment."

The findings, published recently in the Proceedings of the National Academy of Sciences, suggest that this SNP could be a useful marker of prognosis and for guiding therapy in acute leukemia patients.

Specifically, the DNA change caused by the SNP creates a binding site for an activating molecule called RUNX1, which is also involved in the formation of normal
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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

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