We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Evidence for a Mesothelial Origin of Body Cavity Effusion Lymphomas.
- Authors
Sanchez-Martin, David; Uldrick, Thomas S.; Kwak, Hyeongil; Ohnuki, Hidetaka; Polizzotto, Mark N.; Annunziata, Christina M.; Raffeld, Mark; Wyvill, Kathleen M.; Aleman, Karen; Victoria Wang; Marshall, Vickie A.; Whitby, Denise; Yarchoan, Robert; Tosato, Giovanna; Wang, Victoria
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Mesothelial-to-lymphoid transformation is a newly identified in vitro 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.
- Subjects
LYMPHOMAS; LYMPHATIC cancer -- Etiology; KAPOSI'S sarcoma-associated herpesvirus; EPSTEIN-Barr virus; BODY cavities; MIXED infections; POLYMERASE chain reaction; LABORATORY mice
- Publication
JNCI: Journal of the National Cancer Institute, 2017, Vol 109, Issue 9, p1
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djx016