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MicroRNA-TP53 circuit connected to chronic lymphocytic leukemia
Date:1/7/2011

HOUSTON - The interplay between a major tumor-suppressing gene, a truncated chromosome and two sets of microRNAs provides a molecular basis for explaining the less aggressive form of chronic lymphocytic leukemia, an international team of researchers reports today in the Jan. 4 edition of the Journal of the American Medical Association.

"Our findings could reveal new mechanisms of resistance to chemotherapy among leukemia patients as this feedback mechanism could help us differentiate between patients with poor or good prognosis," said co-senior author George Adrian Calin, M.D., Ph.D., associate professor in The University of Texas MD Anderson Cancer Center Department of Experimental Therapeutics and co-director of the Center for RNA Interference and Noncoding RNAs.

B cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia among adults, with an estimated 14,990 new cases in 2010 in the United States. It's caused by aberrant versions of infection-fighting B cell lymphocytes, a white blood cell.

Deletion of the long arm of chromosome 13, called 13q, has been associated with less aggressive, or indolent, CLL. In a series of experiments, a team led by Calin and colleagues at MD Anderson and The Ohio State University uncovered the details of that relationship.

"This finding represents the most detailed pathogenetic mechanism involving microRNAs for any human disease," Calin said. MicroRNAs, or miRNAs, are short, single-stranded bits of RNA that regulate the messenger RNA expressed by genes to tell a cell's protein-making machinery which protein to make.

Deletion of 13q unleashes two proteins known to stymie programmed cell death, or apoptosis, a frontline defense against formation and growth of malignant cells, the researchers found. However, it also leads to increased expression of the tumor suppressor gene TP53, which indirectly reduced levels of another protein associated with poor survival
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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