Lymphoid hyperplasia and lymphoma in KSHV K1 transgenic mice
Zuzana Berkova1, Shu Wang1, Lalit Sehgal1, Keyur Pravinchandra Patel2, Om Prakash3 and Felipe Samaniego1
1Department of Lymphoma and Myeloma, and 2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX and 3Laboratory of Molecular Oncology and Department of Pathology, Ochsner Clinic Foundation, New Orleans, LA, USA
Offprint requests to: Dr. Felipe Samaniego, The University of Texas - MD Anderson Cancer Center, Department of Lymphoma and Myeloma, 1515 Holcombe Blvd. Unit #429, Houston, TX 77030, USA. e-mail: fsamaniego@mdanderson.org
Summary. 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. Histol Histopathol 30, 559-568 (2015)
Key words: KSHV K1, ITAM, Lymphoma, Fas receptor, Apoptosis
DOI: 10.14670/HH-30.559