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

Farzaneh Ghazavi UGent, Emmanuelle Clappier, Tim Lammens UGent, Stefan Suciu, Aurélie Caye, Samira Zegrari, Marleen Bakkus, Nathalie Grardel, Yves Benoit UGent, Odile Minckes, et al. (2015) HAEMATOLOGICA. 100(10). p.1311-1319
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
THERAPY, IKZF1 DELETIONS, IMPACT, TRIAL, IKAROS, GENETIC ALTERATIONS, HODGKIN-LYMPHOMA, ERG DELETION, CHILDHOOD, GENOMIC CHARACTERIZATION
journal title
HAEMATOLOGICA
Haematologica
volume
100
issue
10
pages
1311 - 1319
Web of Science type
Article
Web of Science id
000365775800023
JCR category
HEMATOLOGY
JCR impact factor
6.671 (2015)
JCR rank
4/70 (2015)
JCR quartile
1 (2015)
ISSN
0390-6078
DOI
10.3324/haematol.2015.126953
language
English
UGent publication?
yes
classification
A1
additional info
the last two authors contributed equally to this work
copyright statement
I have retained and own the full copyright for this publication
id
6959433
handle
http://hdl.handle.net/1854/LU-6959433
date created
2015-10-13 15:53:58
date last changed
2017-02-22 13:58:52
@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},
}

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.