Gene Profiles Could Help Cure Kids With Leukemia
Reported March 7, 2005
ORLANDO, Fla. (Ivanhoe Newswire) — Researchers have uncovered new genes that may help explain why 20 percent of children diagnosed with acute lymphoblastic leukemia are resistant to treatment with chemotherapy drugs. This study was presented at the annual meeting of the American Society of Clinical Pharmacology and Therapeutics in Orlando, Fla.
Researcher Mary V. Relling, PharmD, from St. Judes Childrens Research Hospital in Memphis explained that every year in the United States about 2,400 children are diagnosed with ALL. Most of these are toddlers between ages 2 and 3. Chemotherapy cures about 80 percent of ALL cases, but the remaining 20 percent have cancer cells that are resistant to chemotherapy drugs.
Relling and colleagues set out to determine genetic predictors of ALL outcome. Their hope is with knowledge of these genes, doctors could better individualize chemotherapy drugs to maximize cure rates and minimize adverse effects. She says the average ALL patient takes seven to eight drugs and undergoes 120 weeks of chemotherapy.
For the study, researchers isolated leukemia cells from 173 newly diagnosed ALL patients and tested the cells sensitivity to four common chemotherapy drugs. They identified 124 genes that predict resistance to the drugs based on their expression patterns. In addition, they found the expression of the genes correlated with the likelihood of relapse years after treatment.
Children who had resistant patterns of gene expression had a three- to 12-fold higher risk of relapse than those whose cells had a sensitive pattern. Interestingly, say the researchers, the identified genes are involved in a wide range of functions including cell communication, proliferation and development as well as the metabolism of proteins, nucleic acids and carbohydrates.
Relling says only three of the 124 genes had been previously linked with ALL resistance. Therefore, she says the genes uncovered in this study point to new targets for future chemotherapy. However, she points out the importance of understanding this is preliminary research, and future research needs to define whether these are new target genes that can be used to treat ALL patients.
In addition, Relling and colleagues made the discovery that a patients genetics — not the cancer cells genetics — also affect the risk of relapse. To reach this conclusion, they analyzed genetic variations in 246 children with ALL. They found common variations in two genes — glutathione S-transferase and thymidylate synthase — were associated with relapse among patients with higher-risk ALL. These genetic variations may provide tests that allow doctors to fine-tune chemotherapy for each patient.
SOURCE: Amanda Jackson at annual meeting of the American Society for Clinical Pharmacology and Therapeutics in Orlando, Fla., March 2-6, 2005
