Improved risk-stratification and outcome prediction in children with average risk precursor-B acute lymphoblastic leukemia using a 19-microRNA signature

Abstract

Risk stratification has led to a tremendous improvement of the 5-year overall survival rates in childhood acute lymphoblastic leukemia (ALL). The average risk group (AR) where nor favorable nor unfavorable factors are found is the largest patient group, accounting for more than 85% of patients. Despite the good overall survival rate the total number of relapses observed in this AR group is considerable. Genome-wide microRNA (miRNA) profiling on diagnostic bone marrow samples of patients who experienced relapse and patients in continuous complete remission (CCR) (follow-up>6 years) allowed us to identify a 19-microRNA prognostic signature, predictive for relapse within this group. The signature holds an accuracy, sensitivity and specificity of respectively 77 %, 69 % and 84 %. Currently, the signature is evaluated in an independent validation cohort. Notably, many of the miRNAs present in this signature are known oncogenes or tumor suppressor genes. Absence of any other prognostic parameter within this patient group makes the identified signature a unique and powerful tool for further risk-stratification. The method and signature are suitable for laboratory routine testing, and, will be further evaluated in a prospective study