IKZF1 Deletion Subtyping and Outcome Analysis in BCR–ABL1-Negative Pediatric B-Cell Acute Lymphoblastic Leukemia: A Single-Institution Experience from North India
| Autor: | Preity Sharma, Ranjit Kumar Sahoo, Vineet Kumar Kamal, Deepam Pushpam, Sanjeev Gupta, Ritu Gupta, Sameer Bakhshi |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Adolescent Fusion Proteins bcr-abl Outcome analysis India North india Gastroenterology Disease-Free Survival law.invention Ikaros Transcription Factor law Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Internal medicine Humans Medicine Single institution Child Polymerase chain reaction Retrospective Studies Sequence Deletion business.industry Remission Induction Infant Retrospective cohort study Hematology B-cell acute lymphoblastic leukemia Prognosis Subtyping Survival Rate Oncology Child Preschool Female business Haploinsufficiency |
| Zdroj: | Clinical Lymphoma Myeloma and Leukemia. 21:e666-e673 |
| ISSN: | 2152-2650 |
| Popis: | Background IKZF1 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 and Methods This 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. Results Out 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. Conclusion The 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. |
| Databáze: | OpenAIRE |
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