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

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. This trial was registered at www.ClinicalTrials.gov as #NCT00003728.

• Authors: 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
• Journal: Haematologica (Haematologica) Vol. 100 Issue 10 Pg. 1311-9 (Oct 2015) ISSN: 1592-8721 [Electronic] Italy
• PMID: 26137961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Ferrata Storti Foundation.

Chemical References

• Antigens, CD
• BTLA protein, human
• Receptors, Immunologic
• antigens, CD200

Topics

• Adolescent
• Alleles
• Antigens, CD (genetics)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Child
• Child, Preschool
• Chromosome Breakpoints
• Clinical Trials as Topic
• Comparative Genomic Hybridization
• DNA Copy Number Variations
• Female
• Gene Deletion
• Gene Frequency
• Humans
• Infant
• Infant, Newborn
• Kaplan-Meier Estimate
• Male
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, genetics, mortality)
• Prognosis
• Receptors, Immunologic (genetics)
• Recurrence