Array‐based profiling of the lymphoma cell DNA methylome does not unequivocally distinguish primary lymphomas of the central nervous system from non‐CNS diffuse large B‐cell lymphomas

Primary lymphomas of the central nervous system (PCNSL) are diffuse large B‐cell lymphomas (DLBCLs) confined to the central nervous system (CNS). We here performed array‐based DNA methylation analyses of 26 PCNSL and 78 DLBCL and validated our findings in an independent dataset. We identified 2847 CpGs differentially methylated between PCNSL and non‐CNS‐DLBCL. Neither a supervised analysis using these CpGs nor application of 3 CpG classifiers selected for class separation unambiguously separated PCNSL from non‐CNS‐DLBCL. Remarkably, 6/78 non‐CNS‐DLBCL consistently segregated with PCNSL, which displayed molecular features typical for PCNSL. Our findings suggest that a subset of non‐CNS‐DLBCL exists which molecularly resembles PCNSL.     

A case of Burkitt's lymphoma that presented initially with resorption of alveolar bone

A 16-year-old male was evaluated for a 1-month history of alveolar bone resorption, which had been treated with endodontics by a neighborhood dentist. Intraoral examination showed slight gingival swelling and teeth mobility. However, no tumor mass was seen. The panoramic image showed resorption of alveolar bone and loss of teeth lamina dura. Because he complained of general fatigue, he was introduced to the internist. Biopsies of gingiva and bone marrow aspiration revealed a massive proliferation of lymphoblasts expressing CD10, 19, 20 and HLA-DR antigens on the surface. Their karyotypes were abnormal; 46, XY, t (8;14) (q24;q32). Accordingly, he was diagnosed as Burkitt's lymphoma, and received intensive chemotherapy which relieved his symptoms and decreased his tumor. However, his disease soon became refractory to chemotherapy, and he died 11 weeks after the onset.     

Some unusual oral lesions in HIV infection: Comments on the current classification

Of the numerous oral lesions reported in HIV-infected patients, four entities will be discussed in this paper: linear gingival erythema; cystic lymphoid hyperplasia of the parotid gland; oral non-Hodgkin's lymphoma; and oral squamous cell carcinoma. Based on the literature and the author's personal experience, it appears that linear gingival erythema is perhaps a specific HIV-associated periodontal lesion, but that insufficient data are available in the literature yet to classify this periodontal lesion as a lesion that is strongly associated with HIV infection. On the other hand, cystic lymphoid hyperplasia of the parotid gland has been rather widely reported and has characteristic histopathological features that would justify consideration of this lesion as highly indicative of an underlying HIV infection. Oral non-Hodgkin's lymphoma, at present regarded as a lesion ‘strongly associated with HIV infection’, is less characteristic in this respect and should merely be classified as ‘a lesion seen in HIV infection’. Oral squamous cell carcinomas, not included in the most recent International Classification of Oral Manifestations of HIV infection, should be listed in Group 3 of that classification, representing ‘lesions seen in HIV infection’. Further criteria should be developed that will enable distinctions to be made between lesions ‘strongly associated with’, ‘less commonly associated with’, and ‘seen in’ HIV infection.     

自体CIK细胞辅助治疗非霍奇金淋巴瘤患者的临床观察

目的观察细胞因子诱导杀伤细胞(cytokine induced killer cells)辅助治疗非霍奇金淋巴瘤的安全性及近期疗效。方法对6例经病理确诊为非霍奇金淋巴瘤并且存在结外器官侵犯的患者,取其自体外周血单个核细胞,在含10%血浆的RPMI-1640培养基中添加Anti-CD3mAb和rhIL-2联合诱导单个核细胞为CIK细胞,并将细胞进行自体回输。结果CIK细胞输注后可见患者体内CD3 CD56 细胞较前增加,影像学复查显示肿块缩小,治疗过程中主要出现畏寒、发热,未观察到其他明显副作用。结论自体单个核细胞可以高效扩增CIK细胞,回输治疗非霍奇金淋巴瘤安全有效,且无明显毒副作用。     

网状分枝扩增法检测EB病毒基因及临床应用研究

目的应用网状分枝扩增法（RAM）检测NHL外周血EB病毒基因，探讨EB病毒感染与NHL的相关性。方法利用人工合成的EBER-1启动子基因，建立网状分枝扩增检测法，以EB病毒阳性细胞株Raji和EB病毒阴性的人白血病细胞株NB4作对照，检测了NHL患者外周血中EB病毒基因。结果RAM能够检出样品中10个分子的靶基因；120例非霍奇金淋巴瘤（NHL）标本中，76例阳性（63．33％），与PCR方法检出结果相一致。结论RAM技术敏感、特异、简便易行；NHL与EB病毒感染具有较高的相关性。     

AID and TET2 co-operation modulates FANCA expression by active demethylation in diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is traced to a mature B malignance carrying abnormal activation-induced cytidine deaminase (AID) expression. AID activity initially focuses on deamination of cytidine to uracil to generate somatic hypermutation and class-switch recombination of the immunoglobulin (Ig), but recently it has been implicated in DNA demethylation of genes required for B cell development and proliferation in the germinal centre (GC). However, whether AID activity on mutation or demethylation of genes involves oncogenesis of DLBCL has not been well characterized. Our data demonstrate that the proto-oncogene Fanconi anaemia complementation group A (FANCA) is highly expressed in DLBCL patients and cell lines, respectively. AID recruits demethylation enzyme ten eleven translocation family member (TET2) to bind the FANCA promoter. As a result, FANCA is demethylated and its expression increases in DLBCL. On the basis of our findings, we have developed a new therapeutic strategy to significantly inhibit DLBCL cell growth by combination of the proteasome inhibitor bortezomib with AID and TET2 depletion. These findings support a novel mechanism that AID has a crucial role in active demethylation for oncogene activation in DLBCL.     

Clinical characteristics of primary intestinal NK/T cell lymphoma,nasal type: Case series and review of the literature

Background

Primary intestinal NK/T cell lymphoma is rare but aggressive and exhibits a poor prognosis. Little is known about its clinical characteristics because few studies with small sample sizes have been reported.