High tumor necrosis factor-alpha levels in the patients with Epstein-Barr virus-associated peripheral T-cell proliferative disease/lymphoma

We have attempted to find out any relationships between circulating tumor necrosis factor (TNF)-alpha levels and Epstein-Barr virus (EBV) associated peripheral T-cell and NK-cell proliferative disease/lymphoma (PTPD/L) status. The distribution of TNF-alpha level was significantly higher (P<0.05) in patients than in controls. Patients carrying EBV genome in their peripheral T-cells showed higher TNF-alpha levels than the patients with EBV negative peripheral T-cells (P<0.001). Among patients whose peripheral T-cells were positive for EBV genome, TNF-alpha levels between the wild type LMP-1 gene carriers and the 30-bp deletion type LMP-1 gene carriers were compared and the wild type LMP-1 gene carrier group showed significantly higher TNF-alpha levels (P<0.01). As for the outcome of the patients and TNF-alpha levels, significant differences were observed between dead and alive with disease group (P<0.001), and dead and alive with complete remission group (P<0.01). Since circulating TNF-alpha levels in PTPD/L patients correlate with the disease and EBV infection status, it may be possible that monitoring of the TNF-alpha levels will be a useful prognostic marker.     

Differential signaling pathways are activated in the Epstein-Barr virus-associated malignancies nasopharyngeal carcinoma and Hodgkin lymphoma

EBV is associated with the epithelial cancer, nasopharyngeal carcinoma (NPC), and the lymphoid malignancy, Hodgkin lymphoma (HL). The EBV latent membrane proteins 1 and 2A are expressed in these tumors. These proteins activate the phosphatidylinositol 3'-OH kinase (PI3K)/Akt pathway, which is commonly activated inappropriately in malignancy. In this study, the status of Akt activation and its targets, glycogen synthase kinase-3beta (GSK-3beta) and beta-catenin, was investigated in NPC and HL clinical specimens. In the majority of HL and NPC specimens, Akt was activated, indicating an important role for this kinase in the development and/or progression of these tumors. Akt phosphorylates and inactivates GSK-3beta, a negative regulator of the proto-oncoprotein beta-catenin that is aberrantly activated in many cancers. GSK-3beta was phosphorylated and inactivated with concomitant nuclear beta-catenin accumulation in the majority of NPC specimens. The malignant cells of the majority of HL cases, however, did not have inactivated GSK-3beta and lacked nuclear beta-catenin expression. These data indicate that this signaling arm of PI3K/Akt is universal and important in NPC pathogenesis but is apparently not affected in HL. These findings point to a divergence in pathways activated by EBV in different cellular contexts.     

T-cell prolymphocytic leukemia with an unusual phenotype CD4+ CD8+

A patient with T-cell prolymphocytic leukemia (T-PLL) is described. The outcome was poor, with death 8 months after diagnosis, despite several therapeutic interventions. The cells carried both CD4 and CD8 epitopes, but other thymocytic markers were absent. The spleen showed infiltration of CD4+ CD8+ prolymphocytes in the red pulp and in T-cell-dependent areas of the white pulp. Immunologic function studies revealed proliferation after stimulation with mitogens and even several antigens. However, in the mixed lymphocyte culture the T-PLL cells did not proliferate. Cytotoxic T-cells could not be induced. In T-non-T recombination experiments neither helper nor suppressor cell function was found for pokeweed mitogen-dependent plasmablast generation of normal B-cells. Cytogenetically, many abnormalities were found. Among them, 14q+; absence of chromosomes 8, 11, and 22; and the presence of large marker chromosomes and fragments.     

Human immunodeficiency virus-associated T-cell lymphoblastic lymphoma in AIDS

A patient with multiple infections whose serum had antibodies to a human immunodeficiency virus (HIV) developed a T-cell lymphoblastic lymphoma (T11+, Leu-1+, Leu-3a+, TdT+, B1-, common ALL-). Antibodies to human T-lymphotropic virus-I (HTLV-I) were absent. T-cell leukemia-lymphoma may be associated with HIV infection.     

Epstein-Barr virus-associated extranodal NK/T-cell lymphoma following mosquito bites in an elderly patient without prior hypersensitivity

We describe a 73-year-old woman who developed fever and inflammation with ulceration at the site of mosquito bites in the lower thigh. Soon she developed disseminated skin lesions characterized by redness, induration, and local heat. Some lesions showed necrosis and ulceration, including those located in the nasal cavity. She had no history of hypersensitivity to mosquito bites, and the serum IgE concentration was within the reference range. A skin biopsy specimen from the lower thigh adjoining the mosquito bites was diagnosed pathologically as showing extranodal NK/T cell lymphoma, nasal type. Southern analysis of the biopsy specimen showed an oligoclonal band representing Epstein-Barr virus (EBV) DNA. Bone marrow examination revealed infiltration by lymphoma cells and marked hemophagocytosis. The patient underwent three cycles of chemotherapy with carboplatin, etoposide, ifosfamide, and dexamethasone (DeVIC), but died of lymphoma progression during treatment. We speculate that, rather than an allergic reaction, this late-life occurrence of hypersensitivity to mosquito bites might represent lymphoproliferative disease induced by a direct action of mosquito salivary gland secretions on EBV- infected NK cells.     

中线外周T细胞淋巴瘤

目的　总结 13例中线外周T细胞淋巴瘤 (MPTL)探讨其特征、治疗及预后。方法　用病理、免疫酶标方法对 13例MPTL进行确诊 ,采用CHOP方案化疗并观察其预后。结果　 8例CR ,2例PR ,其中 2例CR后复发 ,另 3例NR死亡。结论CHOP方案对MPTL有效。血和尿 β2 MG升高和血清LDH升高应视为预后不良因素。     

Atypical CD8+ cutaneous T-cell lymphoma after immunomodulatory therapy

Systemic immunomodulatory agents have recently been approved for the treatment of rheumatoid arthritis and psoriasis. Although lymphomas are known to emerge in the setting of immunosuppressive therapy, it has not been well described or established for the newer biologic immune response modifiers. Herein, we describe 2 patients who developed unusual CD8+ cutaneous lymphoproliferative disorders after treatment with efalizumab and infliximab. The mechanisms and occurrence of lymphoma after immune response modifiers are discussed.     

Epstein-Barr virus-associated complement-fixing and nuclear antigens in Burkitt lymphoma biopsies

Cells from Burkitt lymphoma (BL) biopsies were examined for Epstein-Barr virus (EBV)-associated antigens by complement fixation (CF) tests and by the anti-complement immunofluorescence (ACIF) test. In CF tests, anticomplementary factors made it difficult to test all the biopsies available. However, biopsies from 19 patients were effectively tested and 12 of these (including two from one patient) contained antigen reacting with a battery of human sera with antibody to EBV but not with sera lacking such antibody. Technical difficulties prevented further characterization of the EBV-related antigens in the biopsies. Application of the ACIF test to BL revealed the presence of EBV-related nuclear antigen in biopsies from 11 of 13 patients. Absorption studies indicated that the nuclear antigens of the biopsies were closely related antigenically to the EBV-determined nuclear antigen (EBNA) previously described in lymphoblastoid cell lines. It is concluded that cells of BL biopsies may contain EBNA in addition to the EBV-related membrane antigen previously described. The results provide further evidence that BL cells from African patients resemble non-producer lymphoblastoid cell lines in containing EBNA and therefore appear to be transformed by EBV.     

外周T细胞淋巴瘤研究进展

 外周T细胞淋巴瘤（PTCL）为一组异质性淋巴细胞恶性增殖性疾病,起源于胸腺后成熟T淋巴细胞或自然杀伤细胞。与B细胞淋巴瘤相比,PTCL侵袭性更强,预后更差。综述PTCL的临床诊断与治疗进展。     

EB病毒感染与T细胞淋巴瘤的发生

EB病毒(EBV)是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞.日前检测发现人类T细胞淋巴瘤也存在EBV感染.近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用.观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制.     

EB病毒感染与T细胞淋巴瘤的发生

EB病毒(EBV)是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞.日前检测发现人类T细胞淋巴瘤也存在EBV感染.近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用.观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制.     

EB病毒感染与T细胞淋巴瘤的发生

EB病毒(EBV)是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞.日前检测发现人类T细胞淋巴瘤也存在EBV感染.近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用.观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制.     

EB病毒感染与T细胞淋巴瘤的发生

EB病毒(EBV)是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞.日前检测发现人类T细胞淋巴瘤也存在EBV感染.近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用.观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制.     

EB病毒感染与T细胞淋巴瘤的发生

EB病毒(EBV)是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞.日前检测发现人类T细胞淋巴瘤也存在EBV感染.近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用.观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制.     

EB病毒感染与T细胞淋巴瘤的发生

EB病毒(EBV)是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞.日前检测发现人类T细胞淋巴瘤也存在EBV感染.近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用.观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制.     

EB病毒感染与T细胞淋巴瘤的发生

EB病毒(EBV)是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞.日前检测发现人类T细胞淋巴瘤也存在EBV感染.近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用.观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制.     

EB病毒感染与T细胞淋巴瘤的发生

 EB病毒（EBV）是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞。目前检测发现人类T细胞淋巴瘤也存在EBV感染。近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用。观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制。     

EB病毒感染与T细胞淋巴瘤的发生

EB病毒(EBV)是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞.日前检测发现人类T细胞淋巴瘤也存在EBV感染.近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用.观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制.