The Icsbp locus is a common proviral insertion site in mature B-cell lymphomas/plasmacytomas induced by exogenous murine leukemia virus.
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.
Ma
Shi Liang
SL
Department of Molecular Biology, University of Aarhus, C.F. Møllers Alle, Bldg. 130, DK-8000 Aarhus C, Denmark.
Sørensen
Annette Balle
AB
Kunder
Sandra
S
Sørensen
Karina Dalsgaard
KD
Quintanilla-Martinez
Leticia
L
Morris
David W
DW
Schmidt
Jörg
J
Pedersen
Finn Skou
FS
D000818:Animals; D001483:Base Sequence; D050835:Interferon Regulatory Factors / Q000235:genetics*; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000472:pathogenicity*; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000821:virology*; D051379:Mice; D010954:Plasmacytoma / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016662:Virus Integration / Q000235:genetics*; D000099185:Interferon Regulatory Factor-8
D050835:Interferon Regulatory Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000099185:Interferon Regulatory Factor-8