淋巴瘤主要组织相容性复合物Ⅰ类分子表达情况的实验研究

目的了解淋巴瘤组织和血液淋巴细胞主要组织相容性复合物Ⅰ(MHCⅠ)类分子的表达情况。方法采用实时荧光定量PCR检测淋巴瘤组织mRNA表达,Westernblot检测淋巴瘤组织蛋白表达,流式细胞仪检测血液淋巴细胞MHCⅠ类分子荧光强度。结果淋巴瘤组织mRNA表达由正常对照组的8.52±0.58下降为1.16±0.16(P<0.01);蛋白表达由正常对照组的16.36±1.06下降为2.35±0.24(P<0.01);血液淋巴细胞MHCⅠ类分子平均荧光强度由正常对照组的426±48下降为268±27(P<0.01),均有统计学差异。结论淋巴瘤组织MHCⅠ类分子mRNA和蛋白表达下降,同时血液淋巴细胞MHCⅠ类分子表达也下降。有可能通过检测血液淋巴细胞MHCⅠ类分子表达下降来辅助早期诊断淋巴瘤。     

Survival prediction and conditional survival of primary central nervous system lymphoma: A population-based study

BackgroundPrimary central nervous system lymphoma is a rare and highly aggressive type of non-Hodgkin lymphoma. This study used population-based data to evaluate the clinical characteristics and prognostic factors of primary central nervous system lymphoma and develop a prediction model to estimate survival.MethodsPatients’ data were extracted from the Surveillance, Epidemiology, and End Results database. Significant prognostic factors were identified using univariate and multivariate Cox regression analyses. Conditional survival estimates were calculated as CS(x y) = S(x + y)/S(X), and a nomogram was built to predict patient prognosis.ResultsIn total, 2563 patients with primary central nervous system lymphoma were included. Multivariate Cox analysis showed that age at diagnosis, sex, histology, tumor site, surgery, chemotherapy, and marital status were independent prognostic factors of overall survival. The 1-year conditional survival increased with time, and our nomogram model showed favorable discriminative ability.ConclusionAt the population level, our study found that gross total resection and chemotherapy improved the prognosis of patients with primary central nervous system lymphoma. However, the prognosis of black patients was poor. Conditional survival provided a more accurate and dynamic survival estimate. Moreover, our nomogram had a good performance and could help predict the overall survival of these patients.     

皮肤T细胞淋巴瘤免疫微环境研究进展

【摘要】 皮肤T细胞淋巴瘤（CTCL）是一组具有不同临床表现、病理学改变、免疫表型和分子生物学特征的异质性肿瘤，其发病机制不完全清楚。越来越多的证据表明，肿瘤免疫微环境的组成和功能对于CTCL的发生发展起着重要作用，深入了解其微环境的组成有助于寻找更有效的抗肿瘤免疫治疗方法，同时帮助临床医生更加准确地判断疾病预后。本文就近年来关于CTCL免疫微环境的基础和临床研究进展作一综述。     

Lymphoma,a great imitator in neurology

The title “great imitator” refers to conditions which can cause varied manifestations and mimic many diseases. Lymphoma is worthy of this title. We describe three cases of lymphoma in which lymphoma mimicked other diseases causing neurological dysfunction, specifically sarcoidosis, vasculitis and infection respectively. Case 1 was a 66-year-old man with subacute progressive diplopia and gait disturbance and investigations revealing a supratentorial para-falcine soft tissue lesion, mid-thoracic cord enhancement and right axillary mass and an elevated serum ACE. Right axillary mass core biopsy was diagnostic of Burkitt lymphoma. Case 2 was a 50-year-old man with several weeks of constitutional symptoms and development of lower limb weakness and numbness, urinary retention and confusion while in hospital. MRI brain demonstrated multi-territory cerebral infarcts. Intravascular lymphoma was diagnosed on random skin biopsy. Case 3 was a 65-year-old man with several weeks of headache and diplopia on a background of previously treated Burkitt lymphoma. CSF analysis showed a lymphocytic pleocytosis and markedly low glucose with cytologic analysis negative for malignancy. Investigations for an infective cause were negative. FDG-PET demonstrated marked, disseminated spinal and cranial leptomeningeal disease and a multi-focal, intra-dural relapse of Burkitt lymphoma was diagnosed. The varied manifestations in our cases demonstrate the ability for lymphoma to mimic infective, inflammatory, granulomatous (including sarcoidosis) and neoplastic aetiologies. An elevated serum ACE appears insufficiently diagnostic to confirm sarcoidosis and tissue for histological examination should be sought whenever possible. When the diagnosis is uncertain, the possibility of this great imitator should be considered, especially for multi-focal disease.     

原发纵隔大B细胞淋巴瘤的研究进展

原发纵隔大B细胞淋巴瘤（PMBCL）是一种原发于纵隔的侵袭性大B细胞淋巴瘤，由于其独特的临床和组织学特征，世界卫生组织淋巴肿瘤分类将PMBCL重新分类为一个单独的实体。PMBCL的诊断主要依赖于病理学特征、影像学检查和临床特征等。当前针对PMBCL的治疗方案有很多种，最常用的是R-CHOP和R-EPOCH方案等。放疗对部分患者有益，但也可以导致远期毒性。新药的研发也在不断进行，包括嵌合抗原受体T细胞疗法、抗程序性死亡受体1药物等，治疗后疗效判断和指导下一步的治疗策略主要依赖PET-CT。     

Status of PI3K/Akt/mTOR Pathway Inhibitors in Lymphoma

The phosphatidylinositol-3-kinase (PI3K) pathway is well known to regulate a wide variety of essential cellular functions, including glucose metabolism, translational regulation of protein synthesis, cell proliferation, apoptosis, and survival. Aberrations in the PI3K pathway are among the most frequently observed in cancer, and include amplifications, rearrangements, mutations, and loss of regulators. As a net result of these anomalies, the PI3K pathway is activated in many malignancies, including in Hodgkin and non-Hodgkin lymphomas, and yields a competitive growth and survival advantage, increased metastatic ability, and resistance to conventional therapy. Numerous inhibitors targeting various nodes in the PI3K pathway are undergoing clinical development, and their current status in lymphoma will be the focus of this review.     

Selective inhibition of EZH2 by ZLD10A blocks H3K27 methylation and kills mutant lymphoma cells proliferation

EZH2 (Enhancer of zeste homolog 2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is involved in repressing gene expression by methylating lysine 27 of histone H3 (H3K27) and regulates cell proliferation. EZH2 overexpression is implicated in tumorigenesis and has been a candidate oncogene in several tumor types. Recently, point mutations of EZH2 at Tyr641 and Ala677 were identified in diffuse large B cell lymphoma and follicular lymphoma, where they drive H3K27 hypertrimethylation and cancer progression. Here, we reported a novel, highly potent and selective small molecule inhibitor of EZH2, ZLD10A, which inhibited wild-type and mutant versions of EZH2 with nanomolar potency and had greater than 1000-fold selectivity against 10 other histone methyltransferases. Our results have shown that the compound suppressed global H3K27 methylation and cause the anti-proliferation effects in a concentration- and time-dependent manner in DLBCL cell lines. These results demonstrated that ZLD10A, as a novel EZH2 inhibitor, could be a potential promising agent for the treatment of EZH2 mutant lymphoma.