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Comparative genomic expression signatures of signal transduction pathways and targets in paediatric Burkitt lymphoma: a Children's Oncology Group report
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Titel: |
Comparative genomic expression signatures of signal transduction pathways and targets in paediatric Burkitt lymphoma: a Children's Oncology Group report |
In: | British Journal of Haematology, 177, 2017, 4, S. 601-611 |
veröffentlicht: |
Wiley
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Umfang: | 601-611 |
ISSN: |
0007-1048 1365-2141 |
DOI: | 10.1111/bjh.14604 |
Zusammenfassung: | <jats:title>Summary</jats:title><jats:p>Burkitt lymphoma (<jats:styled-content style="fixed-case">BL</jats:styled-content>) is the most common histological subtype of non‐Hodgkin lymphoma (<jats:styled-content style="fixed-case">NHL</jats:styled-content>) in children and adolescents. Through the introduction of short intensive multi‐agent chemoimmunotherapy, survival has improved significantly over the past 30 years. 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 <jats:styled-content style="fixed-case">BL</jats:styled-content> (<jats:styled-content style="fixed-case">PEBL</jats:styled-content>) samples from the Children's Oncology Group study (<jats:styled-content style="fixed-case">ANHL</jats:styled-content>01P1) by genomic profiling and selected genes were confirmed by quantitative real time polymerase chain reaction. These results were compared to <jats:styled-content style="fixed-case">PEBL</jats:styled-content> samples from public databases and utilised the Gene Expression Omnibus (<jats:styled-content style="fixed-case">GEO</jats:styled-content>) Series (<jats:styled-content style="fixed-case">GSE</jats:styled-content>) 10172 and 4475 (<jats:italic>n</jats:italic> = 16), and 4732 (<jats:italic>n</jats:italic> = 15). Three hundred and seventy‐six genes (approximately 25%) were similarly expressed among three <jats:styled-content style="fixed-case">PEBL</jats:styled-content> sample groups. Several target genes in Toll‐like receptor signalling, <jats:styled-content style="fixed-case">JAK</jats:styled-content>‐<jats:styled-content style="fixed-case">STAT</jats:styled-content> signalling and <jats:styled-content style="fixed-case">MAPK</jats:styled-content> signalling were significantly overexpressed in <jats:styled-content style="fixed-case">PEBL</jats:styled-content>. In addition, several tyrosine kinases, including Bruton tyrosine kinase, protein tyrosine phosphatase and histone deacetylase inhibitor were highly expressed in <jats:styled-content style="fixed-case">PEBL</jats:styled-content>. These pre‐clinical results suggest that specific signal transduction pathways are overly expressed in <jats:styled-content style="fixed-case">PEBL</jats:styled-content> and several pathways could serve as potential future therapeutic targets.</jats:p> |
Format: | E-Article |
Quelle: | Wiley (CrossRef) |
Sprache: | Englisch |