Acute lymphoblastic leukemia, in which the white blood cells turn cancerous, is the most common cancer of childhood. In 1970, only 30 percent of children could be cured, but chemotherapy treatment has improved to the point where about 80 percent survive and live without disease in the long term. But some children have leukemia cells that resist the chemotherapy drugs. A group of American and European researchers is working on understanding what it is that stops some cells from responding to treatment, to find a way to predict on whom chemotherapy will work best.
What the researchers wanted to know: What genes are involved in drug resistance, and does response to treatment depend on how those genes are expressed?
What they did: The study included 271 children who'd been newly diagnosed with acute lymphoblastic leukemia, in Rotterdam, Hamburg, and Memphis. Most children had the version of the disease that involves B cells. The first part of the study was carried out using bone marrow and blood samples from the 173 European children; researchers tested the leukemia cells for resistance to four drugs (prednisolone, vincristine, asparaginase, and daunorubicin) and used computer models to figure out, for each drug, which genes were involved in drug resistance and drug sensitivity, the opposite of resistance. Then, using what they had learned about genes, they gave each patient in Europe and Tennessee a score based on how resistant their genes should be to drugs and compared that with how well chemotherapy worked.
What they found: The researchers turned up 124 genes involved in resistance to one or more of the four drugs; only three of those genes had been linked to resistance to the drugs before. Children who had many resistance genes were significantly more likely to relapse after treatment. But even children predicted to be highly resistant still had a better than 50 percent chance of survival disease-free.
What the study means to you: It's possible to use this method to predict what children will respond to treatment. Some day, the resistance genes (or their protein products) could make targets for drugs.
Caveats: There were already ways to predict which children will respond to treatment, and more research will be needed to find out if this method is any better.
Find out more: Acute lymphoblastic leukemia, from the National Cancer Institute: www.nci.nih.gov/newscenter/all3
from eMedicine: www.emedicine.com/ped/topic2587.htm
Read the article: Holleman, A., et al. "Gene-Expression Patterns in Drug-Resistant Acute Lymphoblastic Leukemia Cells and Response to Treatment." New England Journal of Medicine. Aug. 5, 2004, Vol. 351, No. 6, pp. 533-542.
Abstract online: http://content.nejm.org