Gene variations may lead to regression in children with ALL

January 19, 2009

Specific genetic mutations have been discovered that may point to a significant chance of relapse in children with acute lymphoblastic leukemia (ALL).

Specific genetic mutations have been discovered that may point to a significant chance of relapse in children with acute lymphoblastic leukemia (ALL). The findings, published online on Jan. 7, will appear in the Jan. 29 issue of the New England Journal of Medicine.

The research was spearheaded by researchers from St. Jude Children's Research Hospital, Memphis, Tenn., the University of New Mexico Cancer Research and Treatment Center, Albuquerque, N.M., and the National Cancer Institute (NCI). The Children's Oncology Group (COG) assessed genetic data on leukemia cells obtained at diagnosis from 221 children with high-risk leukemia (ie, a high chance of relapse) who were treated in another COG study. Analysis involved microarrays and DNA sequencing. Investigators evaluated the DNA of the leukemia cells at diagnosis and then assessed whether any identified genetic changes predicted relapse. To confirm that specific genetic changes were associated with relapse, the scientists also examined a second group of 258 children from St. Jude’s with ALL.

A significant association was found with changes in the IKAROS gene. IKAROS mutations matched up with a subgroup of patients treated in the COG study that had poor prognosis. The significance of these alterations was validated in the independent St. Jude patient group.

"Great progress has been made in recent years in improving the cure rate of childhood ALL,” Stephen Hunger, MD, lead COG investigator, said. “The findings of this study help us further subdivide those patients who are unlikely to be cured, and identify patients in whom different therapies should be tested.”

Researchers warn that more analysis is needed to assess how alterations in the gene, known as IKZF1 or IKAROS, result in leukemia relapse. Such findings may lead to diagnostic testing in the future to measure treatment failure risk. This type of testing to track this genetic marker in ALL patients would enable physicians to more accurately assign patients to the best therapies.