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Variations of the ataxia telangiectasia mutated gene in patients with chronic lymphocytic leukemia lack substantial impact on progression-free survival and overall survival: a Cancer and Leukemia Group B study
- Source :
- Leukemia & Lymphoma. 53:1743-1748
- Publication Year :
- 2012
- Publisher :
- Informa UK Limited, 2012.
-
Abstract
- The impact of mutation of the ATM (ataxia telangiectasia mutated) gene in chronic lymphocytic leukemia (CLL) treatment outcome has not been examined. We studied ATM mutations in 73 patients treated with fludarabine and rituximab. ATM gene mutation analysis was performed using temperature gradient capillary electrophoresis. The impact of detected variants on overall survival (OS) and progression-free survival (PFS) was tested with proportional hazards models. None of the 73 patients demonstrated truncating ATM mutations; 17 (23%, 95% confidence interval 14 – 35%) had non-silent variants (ATM-NSVs), including 13 known ATM polymorphisms and four missense variants. ATM-NSVs were not significantly associated with any baseline characteristics including immunoglobulin heavy chain variable gene (IGVH) status. In multivariable models, no significant differences in complete response (p = 0.70), PFS (p = 0.59) or OS (p = 0.13) were observed. Our data indicate that truncating ATM mutations are rare in patients with CLL. Furthermore, in this dataset, these non-silent variants had limited impact on PFS and OS.
- Subjects :
- Adult
Male
Oncology
Cancer Research
medicine.medical_specialty
Chronic lymphocytic leukemia
DNA Mutational Analysis
Immunoglobulin Variable Region
Mutation, Missense
Cell Cycle Proteins
Ataxia Telangiectasia Mutated Proteins
Kaplan-Meier Estimate
Protein Serine-Threonine Kinases
Biology
Polymorphism, Single Nucleotide
Article
Disease-Free Survival
Antibodies, Monoclonal, Murine-Derived
ATM Gene Mutation
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Outcome Assessment, Health Care
medicine
Humans
Missense mutation
Progression-free survival
Aged
Proportional Hazards Models
Aged, 80 and over
Proportional hazards model
Tumor Suppressor Proteins
Hematology
Middle Aged
medicine.disease
Leukemia, Lymphocytic, Chronic, B-Cell
Fludarabine
DNA-Binding Proteins
Leukemia
Mutation
Immunology
Female
Immunoglobulin Heavy Chains
Rituximab
Vidarabine
medicine.drug
Subjects
Details
- ISSN :
- 10292403 and 10428194
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Leukemia & Lymphoma
- Accession number :
- edsair.doi.dedup.....2072f1338460d20dc3ca3440ea899d90