Tumor cells from approximately 40% of patients with Hodgkin or non-Hodgkin lymphoma express the type II latency Epstein-Barr virus (EBV) antigens latent membrane protein 1 (LMP1) and LMP2, which represent attractive targets for immunotherapy.
To characterize ITAM and CTL motifs of LMP2A and to correlate them with C-terminal variants of LMP1 including the 30-bp deletion variant (LMP1delta), comparative sequence analysis was performed on 76 samples from patients with reactive and malignant lympho-proliferation (infectious mononucleosis, n=21; tonsillar hyperplasia, n=16, chronic lympho-proliferation, n = 9; Hodgkin's disease, n = 8; Non-Hodgkin's lymphoma, n = 5; AIDS-related large-cell lymphoma, n=17).
EBVs detected in lymphocytes in normal gastric mucosa, LCLs in SCID mice and non-Hodgkin's lymphoma were also predominantly affected by type A, wild-type F and LMP-1 gene deletion with few exceptions.
To assess the frequency and molecular polymorphism of malignancy-associated latent membrane protein 1 (LMP1) variants in human immunodeficiency virus type 1 (HIV-1) infection, 94 B-lymphoblastoid cell lines spontaneously derived from peripheral blood mononuclear cells (PBMC) and 30 PBMC samples at seroconversion and later (mean, 55 months) were analyzed by longitudinal comparative sequence analysis in 8 patients progressing to non-Hodgkin's lymphoma (AIDS-NHL), 7 patients to opportunistic infections, and 2 patients with long-term asymptomatic HIV-1 infection.
Tumors from both patients with AIDS-associated non-Hodgkin's lymphoma were EBV-positive and expressed LMP1, whereas tumors from all three patients with Burkitt's tumors were positive for EBV but negative for LMP1.
Of note, deletions in the LMP-1 gene were detected with similar prevalence values in EBV+ Hodgkin's disease (HD) (13 of 30, 43.3%) and non-Hodgkin's lymphoma (NHL) (2 of 5, 40%) cases from HIV-seronegative patients and in HIV-related, EBV+ NHLs (4 of 7, 57.1%).
Small deletions in the carboxy-terminal domain of LMP1 have been recently described in Hodgkin's disease, nasopharyngeal carcinoma, and non-Hodgkin's lymphoma.
Fifty-five cases of non-Hodgkin's lymphoma (NHL) of the upper respiratory tract, comprising 27 sinonasal (SN) and 28 Waldeyer's ring (WR) NHL, were investigated for expression of Epstein-Barr virus (EBV)-encoded EBER transcripts and latent membrane protein-1 (LMP-1) by RNA in-situ hybridization (RISH) and immunohistochemistry, respectively.
Differences in EBV association and LMP-1 expression were found between a major group of HIV-associated systemic NHL with blastic cell morphology, including SNCC lymphoma and its variants, and anaplastic cell lymphomas.