期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 172, 期 3, 页码 428-438出版社
WILEY-BLACKWELL
DOI: 10.1111/bjh.13849
关键词
Burkitt lymphoma; rituximab; array-based comparative genomic hybridization (aCGH); next-generation sequencing; outcome
类别
资金
- European Union's Seventh Framework Programme [306242-NGS-PTL]
- Fundacion-Castellano-Leonesa de Hematologia-y-Hemoterapia (FUCALHH)
- Consejeria de Educacion, Junta de Castilla y Leon [HUS272U13]
- SACYL research projects [GRS1172/A/15, GRS 994/A/14, BIO/SA10/14, BIO/SA31/13]
- Fondo de Investigaciones Sanitarias [FISPI09/01543, FIS-PI12/00281, PI14/01971]
- COST-ActionEuGESMA [BM0801]
- Fundacion Espanola de Hematologia y Hemoterapia (FEHH)
- Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III (ISCIII) [RD12/0036/0069, RD12/0036/0029, RD12/0036/0044]
- Spanish Ministry of Economy and Competitiveness
- European Regional Development Fund (ERDF) 'Una manera de hacer Europa' (Innocampus)
- UPTC, Colombia [223-2011]
- Junta de Castilla y Leon from the ERDF
The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose-Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array-based comparative genomic hybridization (CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next-generation sequencing (NGS). Ninety-seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy (P=0038), shorter progression-free survival (PFS; P=0007) and overall survival (OS; P=0009). The integrative analysis of array-CGH and NGS showed that 263% (5/19) and 368% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P=0011) while TCF3 alterations were associated with shorter OS (P=0032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol.
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