HIV Tat induces a prolonged MYC relocalization next to IGH in circulating B-cells
| Autor: | Stéphanie Bury-Moné, Joëlle Wiels, Martine Raphael, Eric Oksenhendler, Y Bou Saada, Yegor S. Vassetzky, Chrystèle Bilhou-Nabera, Frédéric Subra, Diego Germini, David Boutboul, M. Klibi, M. Lipinski, Sergey V. Razin, A Sukhanova, Olga V. Iarovaia, R El-Amine, Andrey Pichugin, Tatyana Tsfasman |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Immunoglobulin gene Male Cancer Research DNA damage Genes myc Chromosomal translocation Biology Recombination-activating gene Fusion gene 03 medical and health sciences 0302 clinical medicine medicine Humans Gene Aged B-Lymphocytes Hematology Middle Aged medicine.disease Burkitt Lymphoma Lymphoma Leukemia 030104 developmental biology Oncology 030220 oncology & carcinogenesis Gene Products tat Cancer research Female Immunoglobulin Heavy Chains |
| Zdroj: | Leukemia. 31(11) |
| ISSN: | 1476-5551 |
| Popis: | With combined antiretroviral therapy (cART), the risk for HIV-infected individuals to develop a non-Hodgkin lymphoma is diminished. However, the incidence of Burkitt lymphoma (BL) remains strikingly elevated. Most BL present a t(8;14) chromosomal translocation which must take place at a time of spatial proximity between the translocation partners. The two partner genes, MYC and IGH, were found colocalized only very rarely in the nuclei of normal peripheral blood B-cells examined using 3D-FISH while circulating B-cells from HIV-infected individuals whose exhibited consistently elevated levels of MYC-IGH colocalization. In vitro, incubating normal B-cells from healthy donors with a transcriptionally active form of the HIV-encoded Tat protein rapidly activated transcription of the nuclease-encoding RAG1 gene. This created DNA damage, including in the MYC gene locus which then moved towards the center of the nucleus where it sustainably colocalized with IGH up to 10-fold more frequently than in controls. In vivo, this could be sufficient to account for the elevated risk of BL-specific chromosomal translocations which would occur following DNA double strand breaks triggered by AID in secondary lymph nodes at the final stage of immunoglobulin gene maturation. New therapeutic attitudes can be envisioned to prevent BL in this high risk group. |
| Databáze: | OpenAIRE |
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