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.

Boer J.M., Van Der Veer A., Rizopoulos D., Fiocco M., Sonneveld E., De Groot-Kruseman H.A., et al. (2016). Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: An international collaborative study. LEUKEMIA, 30(1), 32-38 [10.1038/leu.2015.199].

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

PALMI, CHIARA;Cazzaniga, G;CONTER, VALENTINO;
2016

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.
Si
Articolo in rivista - Articolo scientifico
Scientifica
Adolescent; Adult; Child; Child, Preschool; Core Binding Factor Alpha 2 Subunit; Humans; Ikaros Transcription Factor; Infant; International Cooperation; Oncogene Proteins, Fusion; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Proportional Hazards Models; Gene Deletion; Hematology; Cancer Research; Anesthesiology and Pain Medicine; Medicine (all)
English
32
38
7
Boer J.M., Van Der Veer A., Rizopoulos D., Fiocco M., Sonneveld E., De Groot-Kruseman H.A., et al. (2016). Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: An international collaborative study. LEUKEMIA, 30(1), 32-38 [10.1038/leu.2015.199].
Boer, J; Van Der Veer, A; Rizopoulos, D; Fiocco, M; Sonneveld, E; De Groot Kruseman, H; Kuiper, R; 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; Venn, N; Sutton, R; Schwab, C; Enshaei, A; Vora, A; Stanulla, M; Schrappe, M; Cazzaniga, G; Conter, V; Zimmermann, M; Moorman, A; Pieters, R; Den Boer, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/149622
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