Clinical significance of TP53, BIRC3, ATM and MAPK-ERK genes in chronic lymphocytic leukaemia: data from the randomised UK LRF CLL4 trial

Despite advances in chronic lymphocytic leukaemia (CLL) treatment, globally chemotherapy remains a central treatment modality, with chemotherapy trials representing an invaluable resource to explore disease-related/genetic features contributing to long-term outcomes. In 499 LRF CLL4 cases, a trial w...

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Veröffentlicht in:	Leukemia 2020-07, Vol.34 (7), p.1760-1774
Hauptverfasser:	Blakemore, Stuart J., Clifford, Ruth, Parker, Helen, Antoniou, Pavlos, Stec-Dziedzic, Ewa, Larrayoz, Marta, Davis, Zadie, Kadalyayil, Latha, Colins, Andrew, Robbe, Pauline, Vavoulis, Dimitris, Forster, Jade, Carr, Louise, Morilla, Ricardo, Else, Monica, Bryant, Dean, McCarthy, Helen, Walewska, Renata J., Steele, Andrew J., Chan, Jacqueline, Speight, Graham, Stankovic, Tanja, Cragg, Mark S., Catovsky, Daniel, Oscier, David G., Rose-Zerilli, Matthew J. J., Schuh, Anna, Strefford, Jonathan C.
Format:	Artikel
Sprache:	eng
Schlagworte:	45 45/22 45/23 631/208/69 631/67/1990/283/1895 692/308/2056 Antineoplastic Combined Chemotherapy Protocols - therapeutic use Ataxia Telangiectasia Mutated Proteins - genetics Baculoviral IAP Repeat-Containing 3 Protein - genetics Biomarkers, Tumor - genetics Cancer Cancer Research Chemotherapy Chronic lymphocytic leukemia Clinical significance Clinical trials Cohort Studies Critical Care Medicine Cyclophosphamide - administration & dosage Extracellular signal-regulated kinase Extracellular Signal-Regulated MAP Kinases - genetics Follow-Up Studies Gene deletion Gene Expression Regulation, Neoplastic Gene mutations Genes Genetic aspects Genetic research Health services Hematology Humans Intensive Internal Medicine Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - mortality Leukemia, Lymphocytic, Chronic, B-Cell - pathology MAP kinase MAP Kinase Signaling System - genetics Markers Medicine Medicine & Public Health Mutation Mutation rates Oncology p53 Protein Prognosis Survival analysis Survival Rate Tumor proteins Tumor Suppressor Protein p53 - genetics Vidarabine - administration & dosage Vidarabine - analogs & derivatives
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Zusammenfassung:	Despite advances in chronic lymphocytic leukaemia (CLL) treatment, globally chemotherapy remains a central treatment modality, with chemotherapy trials representing an invaluable resource to explore disease-related/genetic features contributing to long-term outcomes. In 499 LRF CLL4 cases, a trial with >12 years follow-up, we employed targeted resequencing of 22 genes, identifying 623 mutations. After background mutation rate correction, 11/22 genes were recurrently mutated at frequencies between 3.6% ( NFKBIE ) and 24% ( SF3B1 ). Mutations beyond Sanger resolution (
ISSN:	0887-6924 1476-5551
DOI:	10.1038/s41375-020-0723-2