title: Lymphoid hyperplasia and lymphoma in KSHV K1 transgenic mice.
abstract: Growing evidence supports the involvement of human herpervirus 8, Kaposi's sarcoma associated herpesvirus (KSHV), in the pathology of primary effusion lymphoma, multicentric Castleman's disease, and Kaposi's sarcoma, but the exact mechanism of KSHV contribution to the oncogenic process remains elusive. We studied transgenic mice expressing the ORF K1 of KSHV, whose position in the KSHV genome corresponds to known lymphoproliferative genes of other herpesviruses. K1 protein was previously shown to contain a constitutively active ITAM domain, involved in activation of Akt and pro-survival signaling, and to inhibit Fas-mediated apoptosis by interfering with binding of FasL. All this pointed to a possible role of K1 in the pathogenesis of KSHV-associated cancers. K1 transgenic mice (80-90%) developed lymphoid hyperplasia and splenomegaly at 8 and 10 months of age, 25% had confirmed diagnosis of lymphoma, and 50% developed abdominal and/or hepatic tumors by 18 months of age. Histological examination showed loss of splenic architecture and increased cellularity. Lymph nodes showed disrupted architecture with effaced follicles and other pathological changes, including signs of angiofollicular lymphoid hyperplasia. One of the livers showed signs of angiosarcoma. In summary, our histology results revealed pathological changes in K1 transgenic mice similar to lymphoma, Castleman's disease, and angiosarcoma, suggesting that K1 may contribute to the development of KSHV-associated cancers.
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Berkova
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lalit
authors.initials: L
authors.lastname: Sehgal
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Keyur Pravinchandra
authors.initials: KP
authors.lastname: Patel
authors.affiliation: Laboratory of Molecular Oncology and Department of Pathology, Ochsner Clinic Foundation, New Orleans, LA, USA.
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. fsamaniego@mdanderson.org.
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D005871:Castleman Disease / Q000235:genetics / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D019288:Herpesvirus 8, Human; D006965:Hyperplasia / Q000235:genetics / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology*; D054685:Lymphoma, Primary Effusion / Q000235:genetics / Q000821:virology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016366:Open Reading Frames; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000821:virology; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D060168:Thymocytes / Q000166:cytology; D019014:fas Receptor / Q000737:chemistry
chemical_list: D019014:fas Receptor