Neutropenia is an abnormal reduction in the numbers of immune cells, called neutrophils; the disorder leaves individuals more vulnerable to infections.

The finding means that clinicians can begin treatment sooner and eliminate the cost of this specialized test, which determines if the child carries a variation in the gene UGT1A1 that is linked to this side effect of neutropenia, said Clinton Stewart, Pharm.D., associate member of the St. Jude Department of Pharmaceutical Sciences.

"By giving the drug in small doses for two weeks instead of the standard single large dose once a month, children can begin treatment with irinotecan immediately," said Stewart, first author of a report on this study that appears in the June 20 issue of the "Journal of Clinical Oncology." Irinotecan is used to treat childhood solid tumors such as neuroblastoma, sarcomas and kidney tumors.

"This finding should help clinicians design effective and safe irinotecan treatments for individual children," said Lisa McGregor, M.D., Ph.D., assistant member of the St. Jude Department of Oncology and the report's senior author.

Other authors of this study include John Panetta, Melinda O'Shaughnessy, Stacy Throm, Charles Fraga, Thandranese Owens, Tiebin Liu, Catherine Billups, Carlos Rodriguez-Galindo, Amar Gajjar and Wayne Furman (St. Jude).

This work was supported in part by the National Institutes of Health, a Cancer Center Support Grant and ALSAC.

stjude/

While previous studies have tried to compare gene expression in different types of stem cells, the strategy used in this study was unique. Rather than simply searching for any genes expressed by stem cells, the researchers looked for genes whose expression was also correlated with the master stem cell regulator gene Oct4. They also applied very rigorous analysis methods, using data from StemBase, the largest stem cell gene expression database in the world. Designed by bioinformaticist Dr. Miguel Andrade, the database includes data from thousands of DNA microarrays submitted mainly by scientists in Canada's Stem Cell Network. All data is freely available at www.stembase.

Lead author Ms. Pearl Campbell noted that understanding how stem cells maintain their identity is key to the emerging field of regenerative medicine. "These findings may help us to understand how the key genes which control cell fate are regulated, and how, when dysregulated, they can lead to disease. This may ultimately allow us to develop targeted therapies to stimulate adult stem cells within our own bodies to repair damaged tissues, and may provide further areas of exploration for the treatment of cancer."

plos