Nuclear Excision Repair as a Possible Predictor of Early Relapse in Pediatric ALL
Researchers recently discovered that by testing the level of nucleotide excision repair (NER) gene expression, pediatric oncologists may be able to determine the likelihood of early relapse (less than 3 years) in patients with acute lymphoblastic leukemia (ALL). These findings were published by Ibrahim et al in BMC Medical Genomics.
NER is a major pathway of mammalian DNA repair that is associated with drug resistance. Researchers performed secondary data analysis on two sets of pediatric patients with ALL who had relapsed disease. The patients also had matched diagnosis-relapse gene-expression microarray data. The first group included 49 patients with precursor B-cell ALL (B-ALL) patients, and the second included 27 patients with precursor B-ALL and 14 patients with T-cell ALL. The researchers compared time of diagnosis and relapse between the groups and also looked for early- and late-relapsing subgroups.
Study Findings
Gene expression of the NER pathway was significantly increased upon relapse in patients who took 3 or more years to relapse (P = .007). No such change was evident in patients who relapsed in less than 3 years (P = .180). At diagnosis, the NER gene expression of the early-relapse subpopulation was already significantly elevated over that of the late-relapse group (P < .001). This pattern was validated by a score established by averaging the relative expression of the 20 canonical NER genes. NER score at diagnosis was found to be significantly associated with disease-free survival in precursor B-ALL (P < .001). The authors concluded, “Patients are over two times more likely to undergo early relapse if they have a high NER score at diagnosis (hazard ratio = 2.008, 95% confidence interval = 1.256–3.211),”.
“Our research found a correlation between high NER expression levels and early relapse of ALL among relapsing patients,” said study author Jean Latimer, PhD, Director of the Nova Southeastern University AutoNation Institute for Breast and Solid Tumor Cancer Research and Associate Professor and cancer research scientist, College of Pharmacy, in a statement. “Being able to identify patients with the highest risk of early recurrence who are not detectable using present clinical measures and then treating them with a more targeted therapy is crucial to overcoming the cancer.”
“By being able to accurately predict if a child’s cancer is likely to recur early or not, we may also spare many children who have low NER levels from the most toxic chemotherapy regimens,” concluded Dr. Latimer.
Disclosure: The study authors’ full disclosures can be found at bmcmedgenomics.biomedcentral.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
