The Icsbp locus is a common proviral insertion site in mature B-cell lymphomas/plasmacytomas induced by exogenous murine leukemia virus

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• 作者：Shi Liang Ma ; Annette Balle Sø ; rensen ; Sandra Kunder ; Karina Dalsgaard Sø ; rensen ; Leticia Quintanilla-Martinez ; David W. Morris ; Jö ; rg Schmidt and Finn Skou Pedersen
• 关键词：Murine leukemia virus ; Insertional mutagenesis ; B-cell lymphomas ; Plasmacytoma ; Common integration site
• 刊名：Virology
• 出版年：2006
• 出版时间：1 September 2006
• 年：2006
• 卷：352
• 期：2
• 页码：306-318
• 全文大小：1351 K

文摘

ICSBP (interferon consensus sequence binding protein)/IRF8 (interferon regulatory factor 8) is an interferon gamma-inducible transcription factor expressed predominantly in hematopoietic cells, and down-regulation of this factor has been observed in chronic myelogenous leukemia and acute myeloid leukemia in man. By screening about 1200 murine leukemia virus (MLV)-induced lymphomas, we found proviral insertions at the Icsbp locus in 14 tumors, 13 of which were mature B-cell lymphomas or plasmacytomas. Only one was a T-cell lymphoma, although such tumors constituted about half of the samples screened. This indicates that the Icsbp locus can play a specific role in the development of mature B-lineage malignancies. Two proviral insertions in the last Icsbp exon were found to act by a poly(A)-insertion mechanism. The remaining insertions were found within or outside Icsbp. Since our results showed expression of Icsbp RNA and protein in all end-stage tumor samples, a simple tumor suppressor function of ICSBP is not likely. Interestingly, proviral insertions at Icsbp have not been reported from previous extensive screenings of mature B-cell lymphomas induced by endogenous MLVs. We propose that ICSBP might be involved in an early modulation of an immune response to exogenous MLVs that might also play a role in proliferation of the mature B-cell lymphomas.