Evidence for a Mesothelial Origin of Body Cavity Effusion Lymphomas. (23rd March 2017)

• Record Type: Journal Article
• Authors: Sanchez-Martin, David; Uldrick, Thomas S.; Kwak, Hyeongil; Ohnuki, Hidetaka; Polizzotto, Mark N.; Annunziata, Christina M.; Raffeld, Mark; Wyvill, Kathleen M.; Aleman, Karen; Wang, Victoria; Marshall, Vickie A.; Whitby, Denise; Yarchoan, Robert; Tosato, Giovanna
• Is Part Of: Journal of the National Cancer Institute. Volume 109:Number 9(2017)
• Publication Date: 2017-03-23
• Subjects: Cancer -- Periodicals; Cancer -- Research -- Periodicals; 616.994
• DOI: 10.1093/jnci/djx016
• Languages: English
• ISSNs: 0027-8874

Abstract

Abstract: Background: Primary effusion lymphoma (PEL) is a Kaposi's sarcoma herpes virus (KSHV)–induced lymphoma that typically arises in body cavities of HIV-infected patients. PEL cells are often co-infected with Epstein-Barr virus (EBV). "PEL-like" lymphoma is a KSHV-unrelated lymphoma that arises in body cavities of HIV-negative patients. "PEL-like" lymphoma is sometimes EBV positive. The derivation of PEL/"PEL-like" cells is unclear. Methods: Mesothelial cells were cultured from body cavity effusions of 23 patients. Cell proliferation, cytokine secretion, marker phenotypes, KSHV/EBV infection, and clonality were evaluated by standard methods. Gene expression was measured by quantitative polymerase chain reaction and immunoblotting. A mouse model of PEL (3 mice/group) was used to evaluate tumorigenicity. Results: We found that the mesothelia derived from six effusions of HIV-infected patients with PEL or other KSHV-associated diseases contained rare KSHV + or EBV + mesothelial cells. After extended culture (16–17 weeks), some mesothelial cells underwent a trans-differentiation process, generating lymphoid-type CD45 + /B220 +, CD5 +, CD27 +, CD43 +, CD11c +, and CD3 − cells resembling "B1-cells, " most commonly found in mouse body cavities. These "B1-like" cells were short lived. However, long-term KSHV + EBV − and EBV + KSHV − clonal cell lines emerged from mesothelial cultures from two patients that were clonally distinct from the monoclonal or polyclonal B-cell populations found in the patients' original effusions. Conclusions: Mesothelial-to-lymphoid transformation is a newly identified invitro process that generates "B1-like" cells and is associated with the emergence of long-lived KSHV or EBV-infected cell lines in KSHV-infected patients. These results identify mesothelial cultures as a source of PEL cells and lymphoid cells in humans.