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 journalArticle

Abstract

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 (US)
Pages (from-to)32-38
Number of pages7
JournalLeukemia
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2016

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ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Boer, J. M., Van Der Veer, A., Rizopoulos, D., Fiocco, M., Sonneveld, E., De Groot-Kruseman, H. A., Kuiper, R. P., Hoogerbrugge, P., Horstmann, M., Zaliova, M., Palmi, C., Trka, J., Fronkova, E., Emerenciano, M., Do Socorro Pombo-De-Oliveira, M., Mlynarski, W., Szczepanski, T., Nebral, K., Attarbaschi, A., ... Den Boer, M. L. (2016). Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: An international collaborative study. Leukemia, 30(1), 32-38. https://doi.org/10.1038/leu.2015.199