@article{23a2a039e2524415a26605ac7ffe7c7c,
title = "Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: An international collaborative study",
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.",
author = "Boer, {J. M.} and {Van Der Veer}, A. and D. Rizopoulos and M. Fiocco and E. Sonneveld and {De Groot-Kruseman}, {H. A.} and Kuiper, {R. P.} and P. Hoogerbrugge and M. Horstmann and M. Zaliova and C. Palmi and J. Trka and E. Fronkova and M. Emerenciano and {Do Socorro Pombo-De-Oliveira}, M. and W. Mlynarski and T. Szczepanski and K. Nebral and A. Attarbaschi and N. Venn and R. Sutton and Schwab, {C. J.} and A. Enshaei and A. Vora and M. Stanulla and M. Schrappe and G. Cazzaniga and V. Conter and M. Zimmermann and Moorman, {A. V.} and R. Pieters and {Den Boer}, {M. L.}",
note = "Funding Information: This work was supported by the Dutch Cancer Society (KWF, Grant EMCR 2007-3718 to MLdB and RP; Grant KUN 2009-4298 to RPK and PH), the Sophia Foundation for Scientific Research (SSWO, grant 658 to AvdV and MLdB), the Paediatric Oncology Foundation Rotterdam (to MLdB and RP), the European Union{\textquoteright}s Seventh Framework Program (FP7/2007-2013) under the project European Network for Cancer research in Children and Adolescents (ENCCA, grant agreement HEALTH-F2-2011-261474 to MLdB and GC), the Center for Translational Molecular Medicine BioChip program (to MLdB), the National Health and Medical Research Council and Tour de Cure Foundation in Australia (to RS), the Polish Ministry of Education and Science (project NN407 137738 and project NN407 254440 to WM), the Polpharma Scientific Foundation (to WM), Anniversary of the Austrian National Bank ({\"O}NB, Grant 14133 to KN), Italian Association for Cancer Research (AIRC), the Czech Ministry of Health (NT 12397-4 to EF; NT 13170-4 to MZa) and Fondazione Cariplo and MIUR (to GC). AVM, CJS, AE and AV thank Leukaemia & Lymphoma Research (LLR) for financial support and the UK Cancer Cytogenetic Group (UKCCG) laboratories and the LLR Childhood Leukaemia Cell Bank for providing data and samples. Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited.",
year = "2016",
month = jan,
day = "1",
doi = "10.1038/leu.2015.199",
language = "English (US)",
volume = "30",
pages = "32--38",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "1",
}