Haematologica (Oct 2015)
CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol
- Farzaneh Ghazavi,
- Emmanuelle Clappier,
- Tim Lammens,
- Stefan Suciu,
- Aurélie Caye,
- Samira Zegrari,
- Marleen Bakkus,
- Nathalie Grardel,
- Yves Benoit,
- Yves Bertrand,
- Odile Minckes,
- Vitor Costa,
- Alina Ferster,
- Françoise Mazingue,
- Geneviève Plat,
- Emmanuel Plouvier,
- Marilyne Poirée,
- Anne Uyttebroeck,
- Jutte van der Werff-ten Bosch,
- Karima Yakouben,
- Hetty Helsmoortel,
- Magali Meul,
- Nadine Van Roy,
- Jan Philippé,
- Frank Speleman,
- Hélène Cavé,
- Pieter Van Vlierberghe,
- Barbara De Moerloose
Affiliations
- Farzaneh Ghazavi
- Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Belgium;Center for Medical Genetics, Ghent University Hospital, Belgium
- Emmanuelle Clappier
- Department of Genetics, Robert Debré Hospital, APHP, Paris, France;Hematology University Institute, University Paris-Diderot, Paris, France
- Tim Lammens
- Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Belgium
- Stefan Suciu
- EORTC Headquarters, Brussels, Belgium
- Aurélie Caye
- Department of Genetics, Robert Debré Hospital, APHP, Paris, France;Hematology University Institute, University Paris-Diderot, Paris, France
- Samira Zegrari
- Department of Genetics, Robert Debré Hospital, APHP, Paris, France
- Marleen Bakkus
- Department of Hematology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Belgium
- Nathalie Grardel
- Centre de Biologie Pathologie PM Degand, INSERM U837, Lille, France
- Yves Benoit
- Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Belgium
- Yves Bertrand
- Institute of Hematology and Oncology Paediatrics, Hospices Civils de Lyon, France
- Odile Minckes
- Department of Hematology, CHRU, Caen, France
- Vitor Costa
- Department of Pediatrics, Portuguese Oncology Institute, Porto, Portugal
- Alina Ferster
- Department of Hemato-Oncology, HUDERF, Brussels, Belgium
- Françoise Mazingue
- Department of Pediatric Hematology-Oncology, CHR, Lille, France
- Geneviève Plat
- Department of Hematology, Children’s Hospital, Toulouse, France
- Emmanuel Plouvier
- Department of Hematolo-Oncology, CHRU, Besançon, France
- Marilyne Poirée
- Department of Pediatric Onco-Hematology, Archet University Hospital, Nice, France
- Anne Uyttebroeck
- Department of Pediatric Hematology-Oncology, University Hospitals Leuven, Belgium
- Jutte van der Werff-ten Bosch
- Department of Pediatrics, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Belgium
- Karima Yakouben
- Department of Pediatric Hematology, Robert Debré Hospital, APHP, Paris, France
- Hetty Helsmoortel
- Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Belgium;Center for Medical Genetics, Ghent University Hospital, Belgium
- Magali Meul
- Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Belgium
- Nadine Van Roy
- Center for Medical Genetics, Ghent University Hospital, Belgium
- Jan Philippé
- Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Belgium
- Frank Speleman
- Center for Medical Genetics, Ghent University Hospital, Belgium
- Hélène Cavé
- Department of Genetics, Robert Debré Hospital, APHP, Paris, France;Hematology University Institute, University Paris-Diderot, Paris, France
- Pieter Van Vlierberghe
- Center for Medical Genetics, Ghent University Hospital, Belgium
- Barbara De Moerloose
- Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Belgium
- DOI
- https://doi.org/10.3324/haematol.2015.126953
- Journal volume & issue
-
Vol. 100,
no. 10
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
