High Expression of DNA Repair Genes at Diagnosis Predictive of Early Relapse in Pediatric ALL

Pediatric patients with acute lymphoblastic leukemia (ALL) are more than twice as likely to experience early relapse if they have high levels of expression of genes in the nucleotide excision repair (NER) pathway at diagnosis, according to results from a recent study in BMC Medical Genomics.

NER is a critical pathway in DNA repair in mammals, and alterations in it are associated with drug resistance. Nonetheless, its role in drug resistance and relapse in ALL had not been well characterized.

In this study, researchers secondarily analyzed data from 2 sets of pediatric patients with ALL who eventually relapsed, and who had matched gene expression microarray data at both diagnosis and relapse. One cohort included 49 patients with precursor-B-ALL, and the other cohort included 27 patients with precursor-B-ALL and 14 patients with T-ALL.

Researchers processed the microarray data and extracted expression profiles from the 20 canonical NER genes. NER gene expression was significantly elevated at relapse in patients who relapsed 3 years or more (late relapsers) from diagnosis (P= .007), though no such difference was observed in patients who relapsed less than 3 years (early relapsers) from diagnosis (P= .180).

Additionally, at diagnosis, early relapsers already had a significantly elevated NER gene expression profile compared with late relapsers (P< .001). Researchers then created a NER score by averaging the relative expression pattern of the 20 canonical NER genes, and results indicated that NER score significantly associated with disease-free survival in precursor-B-ALL (P< .001). A high NER score at diagnosis associated with a hazard ratio of 2.008 (95% CI, 1.26-3.21).

“Results from this study may provide a mechanistic basis for a well-established prognostic factor in ALL,” wrote the authors. They concluded that this prognostic evidence could prove a rationale for differential treatment of patients.

Reference

Ibrahim OM, As Sobeai HM, Grant SG, Latimer JJ. Nucleotide excision repair is a predictor of early relapse in pediatric acute lymphoblastic leukemia. BMC Med Genomics.2018;11(1):95.