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Outcome for acute lymphoblastic leukemia linked to gene expression patterns

why patients respond differently to treatment and point to new approaches to overcome these causes of disease relapse."

The researchers tested leukemic cells from 271 children newly diagnosed with ALL for sensitivity to four anti-cancer drugs: prednisolone, vincristine, L-asparaginase and daunorubicin. Using DNA microarray technology, the team determined the levels of expression of thousands of genes in each patient's leukemia cells, and then compared the level of expression (i.e., increased or decreased) of genes in cells that were resistant to each drug to the level of expression of genes in cells that were sensitive to the same drug. The main study group included 173 children enrolled on the ALL-IX Dutch Childhood Oncology Group protocol at the Erasmus University/Sophia Children's Hospital, or on the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia 92 and 97 protocols.

The study found a distinct group of genes that had a specific pattern of expression in leukemia cells according to their sensitivity or resistance to each of the four drugs. In addition, the study identified 123 genes linked to drug resistance and showed that the pattern of expression of these genes is significantly related to the risk of disease relapse.

The ability of these genes to forecast relapse was then validated in a completely independent group of 98 children who were treated with these same drugs, but on a different treatment protocol 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," said Rob Pieters, M.D., chair of Pediatric Oncology/Hematology at Erasmus University, and a senior author of the paper. "This is strong evidence of the link between these r
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
4-Aug-2004


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