Inherited Genes Linked To Toxicity Of Leukemia Therapy

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Genetics
Article Date: 12 May 2007 - 0:00 PDT

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Investigators at St. Jude Children's Research Hospital have discovered inherited variations in certain genes that make children with acute lymphoblastic leukemia (ALL) susceptible to the toxic side effects caused by chemotherapy medications. The researchers showed that these variations, called polymorphisms, occur in specific genes known to influence pharmacodynamics -- how drugs work in the body and how much drug is needed to have its intended effect.

The findings, made during a study of 240 children, are important because these side effects in ALL can be life-threatening and interrupt delivery of treatment, increasing the risk of relapse. The new insights gained in this study could help individualize ALL chemotherapy according to a patient's inherited tendencies to develop toxic reactions to specific drugs.

"Such individualized therapy would eliminate the time-consuming trial-and- error approach to finding the right dose for a patient," said Mary Relling, Pharm.D., chair of the Pharmaceutical Sciences department at St. Jude. "When the results of our findings are translated into routine clinical care, we should see less toxicity among children being treated for ALL." Relling is senior author of a report on this work that appears in the May 15 issue of "Blood."

"Scientists at St. Jude and elsewhere have dramatically improved survival rates from childhood leukemia, but it's still challenging to find the right dose for each patient," said Rochelle Long, Ph.D., director of the National Institutes of Health Pharmacogenetics Research Network. "By finding specific genetic variations linked to how individual patients respond to therapy, this work will make medicines safer and more effective for everyone."

Other authors of this work include Shinji Kishi, Cheng Cheng, Deborah French, Deqing Pei, Nobuko Hijiya, Ching-Hon Pui and William Evans (St. Jude); Soma Das and Edwin Cook (University of Chicago); Carmelo Rizzari (University of Milan, Italy), Gary Rosner (M.D. Anderson Cancer Center, Houston) and Tony Frudakis (DNAPrint Genomics, Sarasota, Fla.).

This work was supported in part by the National Cancer Institute and the National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS) Pharmacogenetics Research Network and Database; a Center of Excellence grant from the State of Tennessee and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay.

St. Jude Children's Research Hospital
http://www.stjude.org

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