Inventors: Prof. Isaac Yaniv and Dr. Smadar Avigad
Background: The treatment of leukemia has improved due to the identification of clinical and biological prognostic factors that define risk subgroups and enable risk-adapted treatment protocols. Currently the risk subgroups are defined by the measurement of minimal residual disease following treatment on days 33 and 78 in patients treated with a BFM treatment protocol. Following high-throughput expression analysis, we identified 2 microRNAs that significantly correlated with the majority of clinical prognostic markers. We then validated the expression levels in a cohort of 101 pediatric precursor B-cell acute lymphoblastic leukemia (ALL) bone marrow samples at diagnosis. We have identified 2 microRNAs that can define the risk subgroups better than the current methods. Low expression of both microRNAs is significantly associated with poor outcome. Patients expressing low levels of both microRNAs have a 10-fold risk to relapse. Furthermore, the significant correlation with outcome was substantiated in an additional cohort treated with a non-BFM protocol. Our results identify the two microRNA as novel biomarkers for outcome in pediatric precursor B-cell ALL patients, regardless of treatment protocol. This may lead to improved risk group stratification already at diagnosis and better relapse free survival.
Technology: Expression analysis by quantitative real-time PCR