Genetic Test Reveals the Reason Young Leukemia Patients Relapse

One of the causes of resistance to cancer treatment in children is now beginning to be elucidated and maybe associated with a specific gene.

Genetic tests show that in acute lymphoblastic leukemia (ALL) patients have a particular form of the activating transcription factor 5 (ATF5) gene, and therefore at higher risk of having a relapse when treated with Escherichia coli asparaginase.

Investigators at the Sainte-Justine University Hospital Research Center, (Montreal, QC, Canada) investigated a study population that consisted of 318 Caucasian children, 97.5% of the patients were of French-Canadian origin from the similar geographical region, diagnosed with ALL at the Hospital Sainte-Justine between January 1989 and July 2005. Genotyping was performed in part by allele specific oligonucleotide hybridization and in part using Sequenom genotyping platform (San Diego, CA, USA). The amplification was not equally successful for all loci analyzed explaining the minor difference in the total number of genotypes.

The scientist observed that E. coli asparaginase therapy was associated with an increase in relapses when administered to patients who had this particular polymorphism of the ATF5 gene. This gene regulates asparagine synthetase, an enzyme that produces asparagine, which in turn feeds cancer cells. The discovery of a form of gene associated with high rates of relapse during treatment with E. coli asparaginase opens the door to the possibility of selecting a type of pharmacological treatment based on a patient's genetic profile, an approach that reflects the shift toward personalized medicine.

Maja Krajinovic, MD, PhD, the lead author of the study said, "If a DNA test detects the implicated polymorphisms in children, it will be possible to predict the risk of relapse or side effects. The clinician can then propose an alternative treatment or adjust the dose accordingly." Since the introduction of combination chemotherapy, the rate of pediatric survival without relapse has risen rapidly to about 80%, yet some patients still resist treatment or present side effects. The study was published on October 4, 2011 in the journal Blood.

Related Links:
Sainte-Justine University Hospital
Sequenom