IKZF1 deletion is an independent predictor of outcome in pediatric acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol

Abstract

IKZF1 gene deletions have been associated with a poor outcome in pediatric precursor B-cell acute lymphoblastic leukemia. To assess the prognostic relevance of IKZF1 deletions for patients treated on Berlin-Frankfurt-Munster Study Group trial ALL-BFM 2000, we screened 694 diagnostic acute lymphoblastic leukemia samples by Multiplex Ligation-Dependent Probe Amplification. Patients whose leukemic cells beared IKZF1 deletions had a lower 5-year event-free survival (0.69+/-0.05 vs. 0.85+/-0.01; p<0.0001) compared to those without, mainly due to a higher cumulative incidence of relapses (0.21+/-0.04 vs. 0.10+/-0.01; p=0.001). Although IKZF1 deletions were significantly associated with the P2RY8-CRLF2 rearrangement, their prognostic value was found independent from this association. Thus, IKZF1 deletion is an independent predictor of treatment outcome and strong candidate marker for integration in future treatment stratification strategies on ALL-BFM protocols.