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CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol

(2015) HAEMATOLOGICA. 100(10). p.1311-1319
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Abstract
DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% +/- 1.2% for patients with deletions versus 83.5% +/- 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23-3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia.
Keywords
THERAPY, IKZF1 DELETIONS, IMPACT, TRIAL, IKAROS, GENETIC ALTERATIONS, HODGKIN-LYMPHOMA, ERG DELETION, CHILDHOOD, GENOMIC CHARACTERIZATION

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Citation

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Chicago
Ghazavi, Farzaneh, Emmanuelle Clappier, Tim Lammens, Stefan Suciu, Aurélie Caye, Samira Zegrari, Marleen Bakkus, et al. 2015. “CD200/BTLA Deletions in Pediatric Precursor B-cell Acute Lymphoblastic Leukemia Treated According to the EORTC-CLG 58951 Protocol.” Haematologica 100 (10): 1311–1319.
APA
Ghazavi, F., Clappier, E., Lammens, T., Suciu, S., Caye, A., Zegrari, S., Bakkus, M., et al. (2015). CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol. HAEMATOLOGICA, 100(10), 1311–1319.
Vancouver
1.
Ghazavi F, Clappier E, Lammens T, Suciu S, Caye A, Zegrari S, et al. CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol. HAEMATOLOGICA. 2015;100(10):1311–9.
MLA
Ghazavi, Farzaneh, Emmanuelle Clappier, Tim Lammens, et al. “CD200/BTLA Deletions in Pediatric Precursor B-cell Acute Lymphoblastic Leukemia Treated According to the EORTC-CLG 58951 Protocol.” HAEMATOLOGICA 100.10 (2015): 1311–1319. Print.
@article{6959433,
  abstract     = {DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8\%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2\% +/- 1.2\% for patients with deletions versus 83.5\% +/- 6.4\% for non-deleted cases (hazard ratio 2.02; 95\% confidence interval 1.23-3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P{\textlangle}0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia.},
  author       = {Ghazavi, Farzaneh and Clappier, Emmanuelle and Lammens, Tim and Suciu, Stefan and Caye, Aur{\'e}lie and Zegrari, Samira and Bakkus, Marleen and Grardel, Nathalie and Benoit, Yves and Minckes, Odile and Costa, Vitor and Ferster, Aline and Mazingue, Fran\c{c}oise and Plat, Genevi{\`e}ve and Plouvier, Emmanuel and Poir{\'e}e, Marilyne and Uyttebroeck, Anne and Van Der Werff-Ten Bosch, Jutte and Yakouben, Karima and Helsmoortel, Hetty and MEUL, MAGALI and Van Roy, Nadine and Philipp{\'e}, Jan and Speleman, Franki and Cav{\'e}, H{\'e}l{\`e}ne and Van Vlierberghe, Pieter and De Moerloose, Barbara},
  issn         = {0390-6078},
  journal      = {HAEMATOLOGICA},
  keyword      = {THERAPY,IKZF1 DELETIONS,IMPACT,TRIAL,IKAROS,GENETIC ALTERATIONS,HODGKIN-LYMPHOMA,ERG DELETION,CHILDHOOD,GENOMIC CHARACTERIZATION},
  language     = {eng},
  number       = {10},
  pages        = {1311--1319},
  title        = {CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol},
  url          = {http://dx.doi.org/10.3324/haematol.2015.126953},
  volume       = {100},
  year         = {2015},
}

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