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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

(2014) LEUKEMIA. 28(1). p.70-77
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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 (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 Delta 4-7 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 Delta 4-7 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.
Keywords
molecular diagnostics, B-cell precursor acute lymphoblastic leukemia, ERG, IKZF1, MINIMAL RESIDUAL DISEASE, TRANSCRIPTION FACTOR ERG, ETS-RELATED GENE, MYELOID-LEUKEMIA, EXPRESSION, CHILDHOOD, CHILDREN, IDENTIFICATION, ABNORMALITIES, TRANSLOCATION

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Chicago
Clappier, E, M-F Auclerc, J Rapion, M Bakkus, A Caye, A Khemiri, C Giroux, et al. 2014. “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.” Leukemia 28 (1): 70–77.
APA
Clappier, E., Auclerc, M.-F., Rapion, J., Bakkus, M., Caye, A., Khemiri, A., Giroux, C., et al. (2014). 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. LEUKEMIA, 28(1), 70–77.
Vancouver
1.
Clappier E, Auclerc M-F, Rapion J, Bakkus M, Caye A, Khemiri A, et al. 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. LEUKEMIA. 2014;28(1):70–7.
MLA
Clappier, E, M-F Auclerc, J Rapion, et al. “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.” LEUKEMIA 28.1 (2014): 70–77. Print.
@article{4267327,
  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 (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{\textlangle}0.001) and frequent IKZF1 Delta 4-7 deletions (37.9\% vs 5.3\%, P{\textlangle}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 Delta 4-7 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.},
  author       = {Clappier, E and Auclerc, M-F and Rapion, J and Bakkus, M and Caye, A and Khemiri, A and Giroux, C and Hernandez, L and Kabongo, E and Savola, S and Leblanc, T and Yakouben, K and Plat, G and Costa, V and Ferster, A and Girard, S and Fenneteau, O and Cayuela, J-M and Sigaux, F and Dastugue, N and Suciu, S and Benoit, Yves and Bertrand, Y and Soulier, J and Cav{\'e}, H},
  issn         = {0887-6924},
  journal      = {LEUKEMIA},
  language     = {eng},
  number       = {1},
  pages        = {70--77},
  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},
  url          = {http://dx.doi.org/10.1038/leu.2013.277},
  volume       = {28},
  year         = {2014},
}

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