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Validation of the United Kingdom copy-number alteration classifier in 3239 children with B-cell precursor ALL
L. Hamadeh, A. Enshaei, C. Schwab, CN. Alonso, A. Attarbaschi, G. Barbany, ML. den Boer, JM. Boer, M. Braun, L. Dalla Pozza, S. Elitzur, M. Emerenciano, L. Fechina, MS. Felice, E. Fronkova, I. Haltrich, MM. Heyman, K. Horibe, T. Imamura, M....
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NV16-32568A
MZ0
CEP Register
Digital library NLK
Full text - Article
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PubMed Central
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- MeSH
- Cytogenetic Analysis MeSH
- Child MeSH
- Genetic Predisposition to Disease MeSH
- Genetic Association Studies MeSH
- Patient Outcome Assessment MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Biomarkers, Tumor * MeSH
- Follow-Up Studies MeSH
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis epidemiology genetics MeSH
- Child, Preschool MeSH
- Prognosis MeSH
- Proportional Hazards Models MeSH
- Population Surveillance MeSH
- DNA Copy Number Variations * MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- United Kingdom MeSH
Genetic abnormalities provide vital diagnostic and prognostic information in pediatric acute lymphoblastic leukemia (ALL) and are increasingly used to assign patients to risk groups. We recently proposed a novel classifier based on the copy-number alteration (CNA) profile of the 8 most commonly deleted genes in B-cell precursor ALL. This classifier defined 3 CNA subgroups in consecutive UK trials and was able to discriminate patients with intermediate-risk cytogenetics. In this study, we sought to validate the United Kingdom ALL (UKALL)-CNA classifier and reevaluate the interaction with cytogenetic risk groups using individual patient data from 3239 cases collected from 12 groups within the International BFM Study Group. The classifier was validated and defined 3 risk groups with distinct event-free survival (EFS) rates: good (88%), intermediate (76%), and poor (68%) (P < .001). There was no evidence of heterogeneity, even within trials that used minimal residual disease to guide therapy. By integrating CNA and cytogenetic data, we replicated our original key observation that patients with intermediate-risk cytogenetics can be stratified into 2 prognostic subgroups. Group A had an EFS rate of 86% (similar to patients with good-risk cytogenetics), while group B patients had a significantly inferior rate (73%, P < .001). Finally, we revised the overall genetic classification by defining 4 risk groups with distinct EFS rates: very good (91%), good (81%), intermediate (73%), and poor (54%), P < .001. In conclusion, the UKALL-CNA classifier is a robust prognostic tool that can be deployed in different trial settings and used to refine established cytogenetic risk groups.
1st Department of Medicine Semmelweis University Budapest Hungary
2nd Department of Paediatrics Semmelweis University Budapest Hungary
Cancer Center for Children Sydney Childrens Hospital Network Westmead NSW Australia
Cancer Cytogenetic Laboratory Schneider Children's Medical Center of Israel Petah Tikva Israel
Children's Cancer Research Institute St Anna Kinderkrebsforschung Vienna Austria
Clinical Research Center National Hospital Organization Nagoya Medical Center Nagoya Japan
Department of Haematology Great Ormond Street Hospital London United Kingdom
Department of Pathology Medical University of Lodz Lodz Poland
Department of Pediatrics Kyoto Prefectural University of Medicine Kyoto Japan
Department of Pediatrics Oncology and Hematology Medical University of Lodz Lodz Poland
Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden
Division of Clinical Research Research Centre Instituto Nacional de Câncer Rio de Janeiro Brazil
Hematology Oncology Department Hospital de Pediatría Prof Dr J P Garrahan Buenos Aires Argentina
Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
References provided by Crossref.org
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