par Clappier, E;Auclerc, M-F;Rapion, J;Bakkus, Marleen;Caye, A;Khemiri, A;Giroux, C;Hernandez, L;Kabongo, E;Savola, S;Leblanc, Thierry;Yakouben, Karima;Plat, G;Costa, V;Ferster, Alina
;Girard, S;Fenneteau, O;Cayuela, J-M;Sigaux, F;Dastugue, Nicole;Suciu, Stefan
;Benoît, Yves;Bertrand, Yves;Soulier, Jean;Cavé, H
Référence Leukemia, 28, 1, page (70-77)
Publication Publié, 2014-01


Référence Leukemia, 28, 1, page (70-77)
Publication Publié, 2014-01
Article révisé par les pairs
Résumé : | Oncogenic subtypes in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are used for risk stratification. However, a significant number of BCP-ALL patients are still genetically unassigned. Using array-comparative genomic hybridization in a selected BCP-ALL cohort, we characterized a recurrent V(D)J-mediated intragenic deletion of the ERG gene (ERG(del)). A breakpoint-specific PCR assay was designed and used to screen an independent non-selected cohort of 897 children aged 1-17 years treated for BCP-ALL in the EORTC-CLG 58951 trial. ERG(del) was found in 29/897 patients (3.2%) and was mutually exclusive of known classifying genetic lesions, suggesting that it characterized a distinct leukemia entity. ERG(del) was associated with higher age (median 7.0 vs 4.0 years, P=0.004), aberrant CD2 expression (43.5% vs 3.7%, P<0.001) and frequent IKZF1 Δ4-7 deletions (37.9% vs 5.3%, P<0.001). However, ERG(del) patients had a very good outcome, with an 8-year event-free survival (8-y EFS) and an 8-year overall survival of 86.4% and 95.6%, respectively, suggesting that the IKZF1 deletion had no impact on prognosis in this genetic subtype. Accordingly, within patients with an IKZF1 Δ4-7 deletion, those with ERG(del) had a better outcome (8-y EFS: 85.7% vs 51.3%; hazard ratio: 0.16; 95% confidence interval: 0.02-1.20; P=0.04). These findings have implications for further stratification including IKZF1 status. |