IKZF1 Deletion Subtyping and Outcome Analysis in BCR–ABL1-Negative Pediatric B-Cell Acute Lymphoblastic Leukemia: A Single-Institution Experience from North India |
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| Institution: | 1. Laboratory Oncology Unit, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India;2. Department of Medical Oncology, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India;3. Division of Epidemiology and Biostatistics, National Institute of Epidemiology, Chennai, India;1. Department of Hematology-oncology, Children''s Hospital of Zhejiang University School of Medicine, the Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, Zhejiang University, Hangzhou, China;2. Department of Infectious Diseases, Children''s Hospital of Zhejiang University School of Medicine, the Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, Zhejiang University, Hangzhou, China;3. Department of Hematology-oncology, Children''s Hospital of Zhejiang University School of Medicine, the Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, Zhejiang University, Hangzhou, China;4. Department of Hematology-oncology, Children''s Hospital of Zhejiang University School of Medicine, the Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, Zhejiang University, Hangzhou, China;5. Department of Hematology-oncology, Children''s Hospital of Zhejiang University School of Medicine, the Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, Zhejiang University, Hangzhou, China;6. Department of Hematology-oncology, Children''s Hospital of Zhejiang University School of Medicine, the Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Zhejiang University, Hangzhou, China;2. Diagnostic Center of Acute Leukemia, Institute of Pharmaceutical Biology, Goethe-University of Frankfurt, Frankfurt am Main, Germany;3. Laboratory of Hematology and Tumor Bank, Cancer Research Institute of Lille, CHRU of Lille, University Lille Nord de France, Lille, France;4. Leukaemia Research Cytogenetics Group, Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University;5. Research Institute Children''s Cancer Center, University Medical Center Hamburg-Eppendorf, Germany;11. Centro Ricerca Tettamanti, Clinica Pediatrica, Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Fondazione MBBM, Monza, Italy;12. Children''s Cancer Institute, Lowy Cancer Research Centre UNSW, Sydney, New South Wales, Australia;8. Hematology and Oncology Department, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina;9. Regional Children''s Hospital No. 1, Yekaterinburg, Russia; Research Institute of Medical Cell Technologies, Yekaterinburg, Russia |
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| Abstract: | BackgroundIKZF1 deletions are associated with adverse outcomes in B-cell acute lymphoblastic leukemia (B-ALL). We assessed the prevalence and clinical impact of functional subtypes of IKZF1 deletions in pediatric BCR–ABL1-negative B-ALL. Patients andMethodsThis retrospective study of IKZF1 deletions was done in cases of pediatric BCR–ABL1-negative B-ALL. The genomic DNA of cases, over a 53-month period, was analyzed using multiplex ligation-dependent probe amplification and multiplex fluorescent polymerase chain reaction. The deletions were divided into functional subgroups: (1) loss-of-function/haploinsufficiency, (2) dominant-negative, and (3) a combination of both types of deletion. The post-induction remission status, event-free survival (EFS), and overall survival (OS) were noted.ResultsOut of 320 cases, 47 (14.7%) had IKZF1 deletions. Thirty-six of the 47 (77%) had loss-of-function deletions, 10 (21%) had dominant-negative deletions, and one (2%) had a combination of both types. The post-induction remission rates in cases with loss-of-function deletions (22/30, 73%; P = .060) and dominant-negative deletions (4/5, 80%; P = .517) were lower compared with those without deletions (215/248, 86.7%). These cases also had worse median EFS: 21.1 months (P = .006) for loss-of-function and 15.4 months (P = .156) for dominant-negative deletions, compared with 46.4 months in cases without IKZF1 deletions. They also had worse median OS: 23.4 months (P = .012) for loss-of-function deletions and 15.7 months (P = .233) for dominant-negative deletions, compared with median not reached in cases without IKZF1 deletions.ConclusionThe IKZF1 deletions were seen in 14.7% of BCR–ABL1-negative pediatric B-ALL. Most of these deletions (77%) were loss-of-function type. The cases with loss-of-function deletions had lower remission rates and poor EFS and OS compared with cases without IKZF1 deletions. A similar trend of poor outcome was seen in the few cases with dominant-negative IKZF1 deletions. |
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