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Genes May Explain Leukemia Treatment Failures

Findings Could Lead to Better Treatment for Patients

WebMD Health News

Aug. 4, 2004 -- A relatively small number of genes may determine whether leukemia treatment succeeds or fails, according to a new study.

Researchers in the U.S. and the Netherlands found the newly identified set of genes were linked to either resistance or sensitivity to the four cancer drugs commonly used to treat acute lymphobastic leukemia (ALL).

The results may help explain why, despite major recent advances in treatment, nearly 20% of children with leukemia still do not respond to treatment.

"We've known for years that certain genetic changes in leukemic cells are associated with a high risk of treatment failure," says researcher William Evans, PharmD, scientific director of St. Jude Children's Research Hospital in Memphis, Tenn., in a news release. "The findings of this study are helping us understand why patients respond differently to treatment and point to new approaches to overcome these causes of disease relapse."

The findings appear in the Aug. 5 issue of the New England Journal of Medicine.

Genes Linked to Drug Resistance

In the study, researchers tested leukemia cells from 173 Dutch children newly diagnosed with leukemia for sensitivity to four common chemotherapy drugs used in leukemia treatment.

Researchers found a particular group of genes that when present in leukemia cells determined their sensitivity or resistance to the four chemotherapy drugs. Of the 124 genes identified, 121 had not been previously associated with resistance to the four chemotherapy drugs tested.

The study also showed that these genes predicted treatment success or relapse in both the 173 Dutch children as well as another group of 98 children with leukemia who were treated with the same drugs at St. Jude.

"The gene expression patterns linked to drug resistance were particularly important since they occurred in both the Rotterdam and the St. Jude patient populations, even though these two groups of children were treated with these drugs in different countries and on different protocols," says Rob Pieters, MD, chair of pediatric oncology/hematology at Erasmus University in Rotterdam, the Netherlands, in the release. "This is strong evidence of the link between these resistance genes and treatment outcome."

Findings Will Lead to Better Treatment

In an editorial that accompanies the study, Naomi J. Winick, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues say that these findings will lead to new, more targeted treatments for leukemia.

"The gene-expression patterns these authors describe can be used to begin to define the mechanisms of resistance and will stimulate the development of alternative treatment strategies, targeted to those with resistant disease identified at diagnosis," write the editorialists.

They say the identification of a gene profile that predicts the outcome of treatment would also allow treatment to be personalized early on and avoid use of unnecessary and ineffective drugs.

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