Genetics and Leukemia
Reported January 29, 2009
(Ivanhoe Newswire) — The cure rate for pediatric acute lymphoblastic leukemia (ALL) has risen from 10 percent in the late 1960s to over 80 percent today. Although there are a higher percentage of cases cured, unexplainable variability still exists in treatment response.
Researchers at St. Jude Children’s Research Hospital in Memphis, Tenn., sought to identify genetic factors that may affect treatment response in children with ALL. The researchers tested single genetic mutations called single nucleotide polymorphisms (SNPs) at the end of chemotherapy in 487 children diagnosed with ALL. They looked for associations with minimal residual disease (MRD), which is marked by leukaemic cells that remain in the patient during treatment or after treatment.
The researchers discovered a total of 102 SNPs associated with MRD. These 102 SNPs remained associated with MRD even after researchers adjusted for race, sex, leukocyte count at diagnosis, age and ALL subgroup. Twenty-one of the SNPs were significantly associated with blood-related relapse and 21 were also significantly associated with antileukemic drug disposition. Overall, 61 percent of the SNPs identified were associated with early response, relapse risk or antileukemic drug disposition.
“Although the acquired genetic characteristics of tumor cells play a critical role in drug responsiveness, our results show that inherited genetic variation of the patient also affects effectiveness of anticancer therapy, and that genome-wide approaches can identify novel and yet plausible pharmacogenetic variation,” study authors were quoted as saying.
SOURCE: The Journal of the American Medical Association, 2009;301:393-403