title: 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-Münster Study Group trial ALL-BFM 2000, we screened 694 diagnostic acute lymphoblastic leukemia samples by Multiplex Ligation-dependent Probe Amplification. Patients whose leukemic cells bore 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 to be independent from this association. Thus, IKZF1 deletion is an independent predictor of treatment outcome and a strong candidate marker for integration in future treatment stratification strategies on ALL-BFM protocols. Clinicaltrials.gov identifier: NCT00430118.
authors.affiliation: Department of Pediatrics, University Medical Centre Schleswig-Holstein, Kiel, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Dörge
authors.forename: Barbara
authors.initials: B
authors.lastname: Meissner
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.forename: André
authors.initials: A
authors.lastname: Schrauder
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bouquin
authors.forename: Denis
authors.initials: D
authors.lastname: Schewe
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.forename: Andrea
authors.initials: A
authors.lastname: Teigler-Schlegel
authors.forename: Richard
authors.initials: R
authors.lastname: Ratei
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: Rolf
authors.initials: R
authors.lastname: Koehler
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.forename: Gunnar
authors.initials: G
authors.lastname: Cario
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: C497239:IKZF1 protein, human; D051740:Ikaros Transcription Factor