Information de reference pour ce titreAccession Number: | 00005597-201401000-00007.
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Author: | Clappier, E 1,2,3; Auclerc, M-F 1,4; Rapion, J 5; Bakkus, M 6; Caye, A 2; Khemiri, A 2; Giroux, C 2; Hernandez, L 1; Kabongo, E 6; Savola, S 7; Leblanc, T 4; Yakouben, K 8; Plat, G 9; Costa, V 10; Ferster, A 11; Girard, S 12; Fenneteau, O 13; Cayuela, J-M 1,3; Sigaux, F 1,3; Dastugue, N 14; Suciu, S 5; Benoit, Y 15; Bertrand, Y 16; Soulier, J 1,3,17; Cave, H 2,3,17,18
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Institution: | (1)U944 INSERM and Hematology laboratory, St-Louis Hospital, APHP, Paris, France; (2)Department of Genetics, Robert Debre Hospital, APHP, Paris, France; (3)Hematology University Institute, University Paris-Diderot, Paris, France; (4)Department of Pediatric Hematology, St-Louis Hospital, APHP, Paris, France; (5)EORTC Headquarters, Brussels, Belgium; (6)Molecular Hematology Laboratory, UZ Brussels, Brussels, Belgium; (7)MRC-Holland, Amsterdam, The Netherlands; (8)Department of Pediatric Hematology, Robert-Debre Hospital, APHP, Paris, France; (9)Department of Pediatric Onco-Hematology, University Hospital Purpan, Toulouse, France; (10)Department of Pediatrics, Portuguese Oncology Institute, Porto, Portugal; (11)Department of Pediatric Onco-Hematology, Children's University Hospital Reine Fabiola, Brussels, Belgium; (12)Hematology Laboratory, IHOP, Lyon, France; (13)Hematology Laboratory, Robert Debre Hospital, APHP, Paris, France; (14)Hematology Laboratory, University Hospital Purpan, Toulouse, France; (15)Department of Pediatric Hematology-Oncology, Ghent University Hospital, Ghent, Belgium and (16)Department of Pediatric Hematology, IHOP and Claude Bernard University, Lyon, France.
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Title: | An intragenic ERG deletion is a marker of an oncogenic subtype of B-cell precursor acute lymphoblastic leukemia with a favorable outcome despite frequent IKZF1 deletions.[Article]
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Source: | Leukemia. 28(1):70-77, January 2014.
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Abstract: | : 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 (ERGdel). 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. ERGdel 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. ERGdel 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 [DELTA]4-7 deletions (37.9% vs 5.3%, P<0.001). However, ERGdel 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 [DELTA]4-7 deletion, those with ERGdel 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.
Copyright (C) 2014 Nature Publishing Group
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Author Keywords: | B-cell precursor acute lymphoblastic leukemia; molecular diagnostics; ERG; IKZF1.
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Language: | English.
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Document Type: | ORIGINAL ARTICLE.
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Journal Subset: | Clinical Medicine. Life & Biomedical Sciences.
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ISSN: | 0887-6924
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NLM Journal Code: | leu, 8704895
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DOI Number: | https://dx.doi.org/10.1038/leu.2...- ouverture dans une nouvelle fenêtre
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