期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 177, 期 4, 页码 601-611出版社
WILEY
DOI: 10.1111/bjh.14604
关键词
gene expression profiles; paediatric Burkitt lymphoma; signal transduction pathways
类别
资金
- Division of Cancer Treatment, National Cancer Institute
- National Institutes of Health, Department of Health and Human Services [CA98543-09, CA98413-09]
- Pediatric Cancer Research Foundation
- St. Baldrick's Foundation
- Hyundai Hope on Wheels
Burkitt lymphoma (BL) is the most common histological subtype of non-Hodgkin lymphoma (NHL) in children and adolescents. Through the introduction of short intensive multi-agent chemoimmunotherapy, survival has improved significantly over the past 30years. However, this successful approach is limited by significant chemotherapy-induced acute toxicity and risk of developing resistant disease, demonstrating the need to identify less toxic and targeted therapies. We analysed the comparative genomic signature and targetable signalling pathways in paediatric BL (PEBL) samples from the Children's Oncology Group study (ANHL01P1) by genomic profiling and selected genes were confirmed by quantitative real time polymerase chain reaction. These results were compared to PEBL samples from public databases and utilised the Gene Expression Omnibus (GEO) Series (GSE) 10172 and 4475 (n - 16), and 4732 (n - 15). Three hundred and seventy-six genes (approximately 25%) were similarly expressed among three PEBL sample groups. Several target genes in Toll-like receptor signalling, JAK-STAT signalling and MAPK signalling were significantly overexpressed in PEBL. In addition, several tyrosine kinases, including Bruton tyrosine kinase, protein tyrosine phosphatase and histone deacetylase inhibitor were highly expressed in PEBL. These pre-clinical results suggest that specific signal transduction pathways are overly expressed in PEBL and several pathways could serve as potential future therapeutic targets.
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