ArticleBlood advances2020
Eμ and 3'RR transcriptional enhancers of the IgH locus cooperate to promote c-myc-induced mature B-cell lymphomas.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Core regions in immunoglobulin heavy chain enhancers essential for survival of non-Hodgkin lymphoma cells are identified by a CRISPR interference screen.Haematologica · 2024Article
- Immunoglobulin germline gene variation and its impact on human disease.Genes and immunity · 2021Review
- Review
- The Eµ-hnRNP K Murine Model of Lymphoma: Novel Insights into the Role of hnRNP K in B-Cell Malignancies.Frontiers in immunology · 2021Review
- Insights about MYC and Apoptosis in B-Lymphomagenesis: An Update from Murine Models.International journal of molecular sciences · 2020Review
- Mouse Models ofFrontiers in immunology · 2020Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous B-cell lymphomas feature translocations linking oncogenes to different locations in the immunoglobulin heavy chain (IgH) locus. During Burkitt lymphoma (BL), IgH breakpoints for c-myc translocation stand either close to JH segments or within switch regions. Transcription, accessibility, and remodeling of the IgH locus are under the control of the 2 potent cis-acting enhancer elements: Eμ and the 3' regulatory region (3'RR). To ensure their respective contributions to oncogene deregulation in the context of the endogenous IgH locus, we studied transgenic mice harboring a knock-in of c-myc in various positions of the IgH locus (3' to JH segments, 5' to Cμ with Eμ deletion and Cα). The observed spectrum of tumors, kinetics of emergence, and transcriptome analysis provide strong evidence that both Eμ and 3'RR deregulate c-myc and cooperate together to promote B-cell lymphomagenesis. Transgenics mimicking endemic BL (with c-myc placed 3' to JH segments) exhibited the highest rate of B-cell lymphoma emergence, the highest Ki67 index of proliferation, and the highest transcriptomic similarities to human BL. The 3'RR enhancer alone deregulated c-myc and initiated the development of BL-like lymphomas, suggesting that its targeting would be of therapeutic interest to reduce c-myc oncogenicity in vivo.
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