Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: an international collaborative study

J M Boer, A van der Veer, D Rizopoulos, M Fiocco, E Sonneveld, H A de Groot-Kruseman, R P Kuiper, P Hoogerbrugge, M Horstmann, M Zaliova, C Palmi, J Trka, E Fronkova, M Emerenciano, M do Socorro Pombo-de-Oliveira, W Mlynarski, T Szczepanski, K Nebral, A Attarbaschi, N VennR Sutton, C J Schwab, A Enshaei, A Vora, M Stanulla, M Schrappe, G Cazzaniga, V Conter, M Zimmermann, A V Moorman, R Pieters, M L den Boer

Research output: Contribution to journalArticlepeer-review


Deletions in IKZF1 are found in ~15% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). There is strong evidence for the poor prognosis of IKZF1 deletions affecting exons 4-7 and exons 1-8, but evidence for the remaining 33% of cases harboring other variants of IKZF1 deletions is lacking. In an international multicenter study we analyzed the prognostic value of these rare variants in a case-control design. Each IKZF1-deleted case was matched to three IKZF1 wild-type controls based on cytogenetic subtype, treatment protocol, risk stratification arm, white blood cell count and age. Hazard ratios for the prognostic impact of rare IKZF1 deletions on event-free survival were calculated by matched pair Cox regression. Matched pair analysis for all 134 cases with rare IKZF1 deletions together revealed a poor prognosis (P<0.001) that was evident in each risk stratification arm. Rare variant types with the most unfavorable event-free survival were DEL 2-7 (P=0.03), DEL 2-8 (P=0.002) and DEL-Other (P<0.001). The prognosis of each type of rare variant was equal or worse compared with the well-known major DEL 4-7 and DEL 1-8 IKZF1 deletion variants. We therefore conclude that all variants of rare IKZF1 deletions are associated with an unfavorable prognosis in pediatric BCP-ALL.

Original languageEnglish
Pages (from-to)32-8
Number of pages7
Issue number1
Publication statusPublished - Jan 2016


  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Core Binding Factor Alpha 2 Subunit/analysis
  • Gene Deletion
  • Humans
  • Ikaros Transcription Factor/genetics
  • Infant
  • International Cooperation
  • Oncogene Proteins, Fusion/analysis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics
  • Prognosis
  • Proportional Hazards Models


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