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

Lookup NU author(s): Claire Schwab, Dr Amir EnshaeiORCiD, Professor Anthony MoormanORCiD


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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 IKZF1deletions is lacking. In an international multi-center study we analyzed the prognostic value of these rare variants in a case-control design. EachIKZF1-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 rareIKZF1 deletions on event-free survival were calculated by matched pair Cox regression. Matched pair analysis for all 134 cases with rare IKZF1deletions 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 IKZF1deletion variants. We therefore conclude that all variants of rare IKZF1deletions are associated with an unfavorable prognosis in pediatric BCP-ALL.

Publication metadata

Author(s): Boer JM, vanderVeer A, Rizopoulos D, Fiocco M, Sonneveld E, deGroot-Kruseman HA, Kuiper RP, Hoogerbrugge P, Horstmann M, Zaliova M, Palmi C, Trka J, Fronkova E, Emerenciano M, Pombo-de-Oliveira MS, Mlynarski W, Szczepanski T, Nebral K, Attarbaschi A, Venn N, Sutton R, Schwab CJ, Enshaei A, Vora A, Stanulla M, Schrappe M, Cazzaniga G, Conter V, Zimmermann M, Moorman AV, Pieters R, denBoer ML

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2015

Pages: 1-7

Online publication date: 11/08/2015

Acceptance date: 13/07/2015

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group


DOI: 10.1038/leu.2015.199


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Funder referenceFunder name
Center for Translational Molecular Medicine BioChip program
Fondazione Cariplo
Leukaemia & Lymphoma Research (LLR)
National Health and Medical Research Council
Italian Association for Cancer Research (AIRC)
Paediatric Oncology Foundation Rotterdam
Polpharma Scientific Foundation
Tour de Cure Foundation in Australia
14133Anniversary of the Austrian National Bank (ONB)
658Sophia Foundation for Scientific Research (SSWO)
EMCR 2007-3718Dutch Cancer Society (KWF)
HEALTH-F2-2011-261474European Union's Seventh Framework Program (FP7) under the project European Network for Cancer research in Children and Adolescents (ENCCA)
NT 13170-4Czech Ministry of Health
KUN 2009-4298Dutch Cancer Society (KWF)
NT 12397-4Czech Ministry of Health