HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients' outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients' quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.

Effects of TNFAIP3 and PDE4B on apoptosis and invasion of tumor cells in diffuse large B cell lymphoma

Objective: To study the effects of TNFAIP3 and PDE4B on apoptosis and invasion of tumor cells in diffuse large B cell lymphoma. Methods: A total of 68 patients who were diagnosed with diffuse large B cell lymphoma in Guangzhou 421 Hospital of PLA between August 2014 and July 2017 were selected as the DLBCL group of the study, and 34 patients who accepted lymph node biopsy due to lymphadenectasis and were diagnosed with reactive lymphoid hyperplasias in Guangzhou 421 Hospital of PLA during the same period were selected as the control group. The expression levels of TNFAIP3, PDE4B, apoptosis genes and invasion genes in lymph node tissue were determined. Results: TNFAIP3, PTEN, PTPL1 and Bax protein expression in lesion tissue of DLBCL group were significantly lower than those of control group whereas PDE4B, c-myc, AURKA, AURKB, PLK1, Ets-1, β-catenin, MMP7, MMP9 and CD44 protein expression were significantly higher than those of control group;PTEN, PTPL1 and Bax protein expression in DLBCL lesions were positively correlated with TNFAIP3 protein expression and negatively correlated with PDE4B protein expression;c-myc, AURKA, AURKB, PLK1, Ets-1, β-catenin, MMP7, MMP9 and CD44 protein expression were negatively correlated with TNFAIP3 protein expression and positively correlated with PDE4B protein expression. Conclusion: The low expression of TNFAIP3 and the high expression of PDE4B in diffuse large B cell lymphoma can antagonize tumor cell apoptosis and promote tumor cell invasion.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography evaluation of subcutaneous panniculitis-like T cell lymphoma and treatment response

Subcutaneous panniculitis-like T cell lymphoma(SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone(commonly known as "GEM-P") as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intraabdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy.

Diffuse large B-cell lymphoma arising from follicular lymphoma with warthin’s tumor of the parotid gland-immunophenotypic and genetic features: A case report

BACKGROUND Warthin’s tumor(WT)is composed of several cysts that are lined with tall,bilayered oncocytic columnar cells and lymphoid stroma.Within WT,the two components rarely transform into carcinoma or lymphoma,and when it does,carcinoma is the most common type.Approximately 28 cases of lymphoma with WT have been reported,most of which were non-Hodgkin lymphomas,and only a few cases were Hodgkin lymphomas.In the present report,we studied a case of diffuse large B cell lymphoma(DLBCL)arising from follicular lymphoma(FL)with WT in the parotid gland and its immunophenotypic and genetic features.CASE SUMMARY A 67-year-old man presented with a slowly enlarging right cheek mass for 12 years,and the mass began to change in size over a 2-mo time period.Over time,the patient felt mild local pain and right cheek discomfort.His medical history included a hepatitis B virus infection for 20 years and 30 years of smoking.Gross examination of the excised specimen showed a gray-red and gray-white appearance and a soft texture lobulated external surface neoplasm that measured 9 cm×8 cm×7 cm and was well circumscribed by relative normal parotid gland tissue.In cross section,the cut surfaces of the neoplasm were multicystic and had a homogeneous scaly appearance.A small fluid was discovered in the cyst.Bilateral oxyphilic,cuboidal or polygonal epithelium cells and lymphoid intraparenchymal components were observed.Many medium-to large-sized lymphoid cells were observed diffusely in part of the neoplasm,and a few secondary lymphoid follicles were observed at the center or edge of the neoplasm.Immunohistochemical staining showed that the columnar oncocytic cells were positive for AE1/AE3;neoplastic cells located in coarctate follicular were positive for CD20,Pax-5,bcl-2 and bcl-6;and the adjacent diffusely medium-to large-sized lymphoid cells were positive for Pax-5,bcl-6,CD20,MUM-1,bcl-2 and CD79a.The bcl-6(3q27)break-apart rearrangement was observed,and an Epstein Barr virus test was negative in the tumor cells.The patient survived 6 months after being diagnosed without any treatment.CONCLUSION WT-associated lymphoma is a very rare neoplasm in the parotid gland.Most cases are B cell non-Hodgkin lymphomas and involve middle-age and older males.This case highlights the extremely rare association of DLBCL arising from FL with WT and the importance of deliberate evaluation of the WT intraparenchymal stroma.Molecular detection techniques have potential advantages in the diagnosis of lymphoma with WT.

Correlation of PI3K/Akt signaling pathway with cell apoptosis and invasion in mantle cell lymphoma

Objective: To study the correlation of PI3K/Akt signaling pathway with cell apoptosis and invasion in mantle cell lymphoma. Methods: A total of 38 patients who were diagnosed with mantle cell lymphoma in Xijing Hospital Affiliated to the Fourth Military Medical University between June 2014 and March 2017 were selected as the MCL group of the research, 55 patients who were diagnosed with reactive lymphoid hyperplasia in Xijing Hospital Affiliated to the Fourth Military Medical University during the same period were selected as the control group of the research, and lymph node tissue was collected to detect the protein expression of p-PI3K and p-AKT as well as the mRNA expression of apoptosis genes and invasion genes. Results: p-PI3K and p-AKT protein expression as well as SOX11, cyclinD1, TNFAIP3, XIAP, PCNA, MMP2, MMP7, MMP9 and VEGF mRNA expression in lymph node of MCL group were significantly higher than those of control group while TNFAIP3 mRNA expression was significantly lower than that of control group;SOX11, cyclinD1, XIAP, PCNA, MMP2, MMP7, MMP9 and VEGF mRNA expression in MCL lymph node with high p-PI3K expression were significantly higher than those in MCL lymph node with low p-PI3K expression while TNFAIP3 mRNA expression was significantly lower than that in MCL lymph node with low p-PI3K expression. Conclusion: The activation of PI3K/Akt signaling pathway in mantle cell lymphoma is closely related to the tumor cell apoptosis disorder and invasion enhancement.

Disseminated soft tissue diffuse large B-cell lymphoma involving multiple abdominal wall muscles:A case report

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common subtype of non�Hodgkin lymphoma,and patients with DLBCL typically present rapidly growing masses.Lymphoma involving muscle is rare and accounts for only 5%;furthermore,multiple muscles and soft tissue involvement of DLBCL is unusual.Due to unusual clinical manifestation,accurate diagnosis could be delayed.CASE SUMMARY A 61-year-old man complained of swelling,pain and erythematous changes in the lower abdomen.Initially,soft tissue infection was suspected,however,skin lesion did not respond to antibiotics.18Fluoro-2-deoxy-D-glucose(18F-FDG)positron emission tomography-computed tomography demonstrated FDG uptake not only in the skin and subcutaneous tissue of the abdomen but also in the abdominal wall muscles,peritoneum,perineum,penis and testis.DLBCL was confirmed by biopsy of the abdominal wall muscle and subcutaneous tissue.After intensive treatment including chemotherapy with rituximab,cyclophosphamide,doxorubicin,vincristine and prednisolone,central nervous system prophylaxis(intrathecal injection of methotrexate,cytarabine and hydrocortisone)and orchiectomy,he underwent peripheral blood stem cell mobilization for an autologous hematopoietic stem cell transplantation.Despite intensive treatment,the disease progressed rapidly and the patient showed poor outcome(overall survival,9 mo;disease free survival,3 mo).CONCLUSION The first clinical manifestation of soft tissue DLBCL involving multiple muscles was similar to the infection of the soft tissue.

Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement

AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.

苍术素调节RhoA/ROCK信号通路对弥漫大B细胞淋巴瘤细胞恶性生物学行为的影响

目的:探讨苍术素(ATR)调节Ras同源基因家族成员A(RhoA)/Rho相关卷曲螺旋形成蛋白激酶(ROCK)信号通路对弥漫大B细胞淋巴瘤(DLBCL)细胞恶性生物学行为的影响。方法:常规培养DLBCL细胞SUDHL-4,将其随机分为对照组、低浓度ATR组(ATR-L组,5μmol/L ATR)、中浓度ATR组(ATR-M组,10μmol/L ATR)、高浓度ATR组(ATR-H组,20μmol/L ATR)和高浓度ATR+RhoA激活剂U46619组(ATR+U46619组,20μmol/L ATR+10 nmol/L U46619)。CCK-8法测定细胞增殖活性。划痕实验检测细胞迁移能力。Transwell实验测定细胞侵袭能力。流式细胞术检测细胞凋亡率。实时荧光定量PCR(RT-qPCR)法测定细胞中RhoA、ROCK1 mRNA表达。免疫印迹法(Western blot)测定各组细胞B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、RhoA、ROCK1蛋白表达。结果:与对照组比较,ATR-M组、ATR-H组SUDHL-4细胞OD450值(48、72 h)、细胞迁移率、细胞侵袭数目、RhoA、ROCK1 mRNA和蛋白表达、Bcl-2蛋白表达降低,细胞凋亡率、Bax蛋白表达升高(均P<0.05)。RhoA激活剂U46619减弱了ATR对DLBCL细胞恶性生物学行为的抑制作用。结论:ATR可能通过下调RhoA/ROCK信号通路抑制DLBCL细胞恶性生物学行为。

Hepatitis viruses and non-Hodgkin's lymphoma: A review

Non-Hodgkin's lymphoma(NHL) is among the haematological malignancies with high prevalence worldwide, causing estimated 355 900 new cases and 191 400 deaths in 2008. High prevalence of NHL is documented in economically more developed areas while low prevalence is observed in less developed areas of the globe. A wide array of environmental factors have been reported to be either directly involved or in modifying the risk of NHL development. In addition to these factors, a number of infectious agents, chiefly viruses have also been implicated in the development of NHL. This article reviews the available literature to discuss the role of hepatitis viruses in NHL development, possible mechanisms of lymphomagenesis and also identify the areas in which further research is required to better understand this disease. A brief discussion on the clinical aspects such as classification, staging, treatment approaches have also been included in this article.

CAR-T细胞免疫疗法在B细胞非霍奇金淋巴瘤中的应用进展

嵌合抗原受体T(CAR-T)细胞疗法是近年来迅速发展的免疫治疗新方法。相对于其他疗法,CAR-T疗法在高危及复发/难治性B细胞非霍奇金淋巴瘤(B-NHL)患者中具有显著优势。目前多种抗CD-19 CAR-T细胞已被FDA批准用于B-NHL的治疗,如阿基仑赛、司利弗明、利基迈仑赛、贝林妥欧单抗。除此之外,许多研究正在积极探索和开发不同靶点的CAR-T细胞,它们在B-NHL的治疗中表现出巨大的潜力。本文就CAR-T在常见B-NHL中的最新应用研究进展作一综述。

血清乳酸脱氢酶、β_(2)-微球蛋白及铁蛋白水平与侵袭性B细胞淋巴瘤患者预后的关系

目的探讨血清乳酸脱氢酶(LDH)、β_(2)-微球蛋白(β_(2)-MG)及铁蛋白水平与侵袭性B细胞淋巴瘤患者预后的关系。方法选取60例侵袭性B细胞淋巴瘤患者,均接受利妥昔单抗+环磷酰胺+表柔比星+长春新碱+泼尼松(R-CHOP)方案化疗,治疗4个疗程后评估临床疗效,检测治疗前后患者血清LDH、β_(2)-MG、铁蛋白水平。随访3年,比较不同预后侵袭性B细胞淋巴瘤患者治疗4个疗程后血清LDH、β_(2)-MG、铁蛋白水平,其与患者预后的相关性采用Spearman秩相关分析。结果60例侵袭性B细胞淋巴瘤患者化疗4个疗程后,完全缓解38例,部分缓解7例,疾病稳定4例,疾病进展11例,疾病控制率为81.67%(49/60)。治疗4个疗程后,侵袭性B细胞淋巴瘤患者血清LDH、β_(2)-MG、铁蛋白水平均明显低于治疗前,差异均有统计学意义(P﹤0.01)。随访3年,所有患者均无失访,生存43例,死亡17例。生存患者治疗4个疗程后血清LDH、β_(2)-MG、铁蛋白水平均明显低于死亡患者,差异均有统计学意义(P﹤0.01)。Spearman秩相关分析结果显示,血清LDH、β_(2)-MG、铁蛋白水平与侵袭性B细胞淋巴瘤患者的预后生存均呈负相关(r=-0.718、-0.823、-0.753,P﹤0.05)。结论血清LDH、β_(2)-MG、铁蛋白水平与侵袭性B细胞淋巴瘤患者的预后生存均呈负相关,有助于临床对患者的预后进行客观评价。

长链非编码RNA人类白细胞抗原复合体18通过微RNA-497-5p/细胞周期蛋白E1轴调节弥漫性大B细胞淋巴瘤的增殖、凋亡和侵袭

目的 探讨长链非编码RNA人类白细胞抗原复合体18(lncRNA HCG18)调控微RNA-497-5p(miR-497-5p)/细胞周期蛋白E1(CCNE1)轴对弥漫性大B细胞淋巴瘤(DLBCL)细胞增殖、凋亡和侵袭的影响。方法 实时荧光定量PCR(qRT-PCR)、蛋白质印迹法分别检测2018年5月至2021年5月收集的恩施土家族苗族自治州中心医院DLBCL病人淋巴组织、良性淋巴结增生病人的淋巴组织、人正常B细胞永生化细胞HMy2.CIR、DLBCL细胞系SU-DHL-1、OCI-LY8、U2932中HCG18、miR-497-5p表达及CCNE1蛋白表达,将OCI-LY8细胞分为Ct组(正常培养的OCI-LY8细胞)、pcDNA组(细胞转染过表达物阴性对照)、pcDNA-HCG18组(细胞转染HCG18过表达物)、si-NC组(细胞转染小干扰RNA阴性对照)、si-HCG18组(细胞转染HCG18小干扰RNA)、si-HCG18+inhibitorNC组(细胞转染HCG18小干扰RNA和抑制物阴性对照)、si-HCG18+miR-497-5p inhibitor组(细胞转染HCG18小干扰RNA和miR-497-5p抑制物),CCK-8法检测细胞增殖,流式细胞术检测细胞凋亡,Transwell检测细胞侵袭,蛋白质印迹法检测CCNE1、增殖细胞核抗原(PCNA)、Bcl-2相关X蛋白(Bax)、基质金属蛋白酶9(MMP-9)蛋白表达,双萤光素酶验证HCG18与miR-497-5p、miR-497-5p与CCNE1的关系。结果 在DLBCL淋巴组织和细胞中,HCG18、CCNE1蛋白高表达,miR-497-5p低表达,且在OCI-LY8细胞中HCG18、CCNE1蛋白表达上调最高,miR-497-5p表达下调最多(P<0.05),因此,以OCI-LY8细胞进行后续研究,与si-NC组比较,si-HCG18组HCG18(0.26±0.03比1.01±0.01)、CCNE1蛋白(0.45±0.03比1.44±0.19)表达降低,miR-497-5p(1.95±0.14比1.03±0.02)表达升高(P<0.05),与pcDNA组比较,pcDNA-HCG18组HCG18(1.96±0.23比1.02±0.01)、CCNE1蛋白(2.33±0.21比1.42±0.18)表达升高,miR-497-5p(0.28±0.02比1.02±0.02)表达降低(P<0.05),与siHCG18组、si-HCG18+inhibitor NC组比较,miR-497-5p表达降低(1.21±0.09比1.95±0.14、1.94±0.13),CCNE1蛋白(0.87±0.08比0.45±0.03、0.44±0.04)表达上调(P<0.05),沉默HCG18可抑制OCI-LY8细胞增殖、侵袭行为及PCNA、MMP-9蛋白表达,诱导细胞凋亡及Bax蛋白表达,而上调HCG18则呈相反趋势,下调miR-497-5p逆转了沉默HCG18对OCI-LY8细胞增殖、侵袭、凋亡的影响,HCG18靶向调控miR-497-5p/CCNE1。结论 沉默HCG18可能通过调控miR-497-5p/CCNE1抑制OCI-LY8细胞增殖、侵袭,诱导细胞凋亡。

DLBCL患者血Th22细胞、IL-22水平及IL-22对DLBCL细胞株增殖和侵袭的影响

目的分析弥漫性大B细胞淋巴瘤(DLBCL)患者血辅助性T细胞22(Th22)细胞、白细胞介素-22(IL-22)水平及IL-22对DLBCL细胞株增殖和侵袭的影响。方法选择DLBCL患者40例(DLBCL组),按照临床分期分为不同亚组;另选同期体检健康者40例为对照组。流式细胞术检测各组Th22细胞比例,ELISA检测各组IL-22蛋白水平。MTT实验检测DLBCL细胞增殖情况,Transwell实验检测DLBCL细胞侵袭情况。结果与对照组比较,DLBCL组Th22细胞比例和IL-22水平升高;与Ⅰ~Ⅱ期比较,Ⅲ~Ⅳ期Th22细胞比例和IL-22水平升高(P<0.05)。化疗后Th22细胞比例低于化疗前,复发者Th22细胞比例高于新诊患者和对照组(P<0.05)。MTT和Transwell实验结果显示,IL-22促进DLBCL细胞的增殖和侵袭(P<0.05)。结论DLBCL患者Th22细胞比例及其细胞因子IL-22水平升高,IL-22促进DLBCL细胞增殖和侵袭,为DLBCL研究提供新策略。

Skp2和p27^(kip1)蛋白在B细胞性非霍奇金淋巴瘤中的表达、定位及意义

目的探讨B细胞性非霍奇金淋巴瘤(B-NHL)组织中Skp2和p27kip1蛋白的表达、定位及意义。方法用免疫组织化学方法检测72例B-NHL和14例反应性增生淋巴结组织Skp2、p27kip1蛋白及细胞增殖指标Ki-67的表达情况,结合病理资料进行统计分析;用免疫荧光双标记技术检测淋巴瘤Raji细胞株Skp2和p27kip1蛋白的定位情况。结果Skp2蛋白在B-NHL组织中的表达高于反应性增生的淋巴结(不含生发中心),在侵袭性B-NHL组织中的表达高于惰性组;p27kip1蛋白在B-NHL组织中的表达低于反应性增生淋巴结(不含生发中心),在侵袭性B-NHL组织中的表达低于惰性组;Skp2蛋白主要在Raji细胞的胞浆中表达,p27kip1蛋白主要表达于胞核。结论在B-NHL组织中,Skp2的高表达和p27kip1的低表达可能与其发生发展有关;Skp2和p27kip1在Raji细胞中的亚细胞定位与其生物学功能一致。

LncRNA ZEB1-AS1对B细胞非霍奇金淋巴瘤增殖和凋亡的影响及其下游调控网络的分析

目的探讨长链非编码RNA(lncRNA)ZEB1-AS1对B细胞非霍奇金淋巴瘤(B-cell non-Hodgkin′s lymphoma,B-NHL)细胞增殖和凋亡的影响,构建lncRNA、miRNA、mRNA相关竞争性内源RNA(ceRNAs)网络。方法采用Cox回归模型筛选GEO数据集(GSE31312)中与弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)预后相关的lncRNAs。采用慢病毒转染技术建立ZEB1-AS1敲低的B-NHL细胞模型,采用CCK-8法和流式细胞术分别检测敲低ZEB1-AS1及不同浓度(50 ng/mL、100 ng/mL、200 ng/mL、400 ng/mL)多柔比星(doxorubicin,Dox)处理后的细胞增殖与凋亡情况。构建以ZEB1-AS1为节点的lncRNA-miRNA-mRNA ceRNA调控网络,利用GO、KEGG和PPI分析该调控网络下游相关的核心mRNA及其功能。结果共筛选了20个高风险lncRNAs。预测与ZEB1-AS1有相互结合的miRNA 4个,与ZEB1-AS1呈共表达关系又与miRNA相结合的潜在下游mRNA 1208个,以此构建lncRNA-miRNA-mRNA调控网络及PPI调控网络。在体外实验中,与空载组相比,敲低ZEB1-AS1可显著抑制细胞增殖和促进细胞凋亡(均P<0.05),敲低ZEB1-AS1+Dox作用对抑制淋巴瘤细胞增殖和促进细胞凋亡有协同作用。结论ZEB1-AS1敲低可抑制B-NHL细胞增殖和促进细胞凋亡,且可能增强Dox的药物敏感性;以ZEB1-AS1为节点构建的ceRNA调控网络,可能是DLBCL重要的调控机制和诊疗靶点。

巨噬细胞来源的外泌体对弥漫大B细胞淋巴瘤增殖、迁移、侵袭和凋亡的影响

目的探讨巨噬细胞来源的外泌体对弥漫大B细胞淋巴瘤(DLBCL)增殖、迁移、侵袭和凋亡的影响。方法构建体外巨噬细胞极化模型;提取外泌体,以加外泌体的DLBCL细胞作为外泌体组,以未加外泌体的DLBCL细胞作为对照组;采用透射电镜检测外泌体形态;采用纳米颗粒跟踪分析技术检测外泌体粒径与水平;采用免疫荧光法检测外泌体传递;采用CCK-8法检测人DLBCL细胞系U2932细胞增殖;采用细胞划痕试验检测U2932细胞迁移;采用Transwell法检测U2932细胞侵袭;采用流式细胞术检测U2932细胞凋亡。结果外泌体水平为(5.27±0.36)×10^(10)particles/mL,平均粒径为121.69 nm,单峰,呈正态分布,直径50~150 nm,其密度约为(1.15±0.03)g/mL。与对照组比较,外泌体组在人DLBCL细胞和巨噬细胞株RAW264.7细胞中的传递均明显增多,差异均有统计学意义(P<0.05);外泌体组人DLBCL细胞系U2932细胞增殖、迁移和侵袭能力均明显高于对照组,差异均有统计学意义(P<0.05);外泌体组人DLBCL细胞系U2932细胞凋亡能力明显低于对照组,差异有统计学意义(P<0.05)。结论巨噬细胞来源的外泌体可以促进人DLBCL细胞系U2932细胞的增殖、迁移和侵袭,并抑制其凋亡,为进一步研究巨噬细胞来源外泌体在人DLBCL发生和发展中的相关机制提供了一定的理论基础。

前清蛋白对自体移植治疗B细胞非霍奇金淋巴瘤患者预后的影响分析

目的 探讨前清蛋白水平等因素对经自体造血干细胞移植的B细胞非霍奇金淋巴瘤患者预后的影响。方法 回顾性分析2006-2017年于陆军军医大学第一附属医院接受自体造血干细胞移植治疗的107例B细胞非霍奇金淋巴瘤患者的临床资料,通过Kaplan-Meier生存分析、Log-rank检验和Cox比例风险回归模型分析患者预后及预后影响因素。结果 107例患者移植后的中位随访时间为52.0个月,3年无进展生存率及总生存率分别为70.0%及79.5%。低前清蛋白组无进展生存率及总生存率与高前清蛋白组比较差异均有统计学意义(P=0.002、0.015)。多因素Cox回归分析提示前清蛋白低于0.15 g/L为影响无进展生存率的独立危险因素(HR=3.42,95%CI:1.47~7.95,P=0.004),前清蛋白低于0.15 g/L(HR=3.39,95%CI:1.28~8.94,P=0.014)及总蛋白水平低于60 g/L(HR=4.33,95%CI:1.68~11.14,P=0.002)为影响总生存率的独立危险因素。结论 自体造血干细胞移植前血清前清蛋白水平低与B细胞非霍奇金淋巴瘤患者预后不良相关。

骨髓涂片形态对弥漫性大B细胞淋巴瘤骨髓侵犯的诊断价值

目的探讨骨髓涂片形态对弥漫性大B细胞淋巴瘤(DLBCL)骨髓侵犯的诊断价值。方法回顾性分析2010年1月至2021年4月本院收治的2100例DLBCL患者的临床资料,观察患者骨髓涂片形态学,比较骨髓活检与实验室检测结果及DLBCL骨髓侵犯涂片和活检的一致性。结果骨髓活检显示,发生骨髓侵犯患者235例,其中包括结旁型患者125例,散在分布型患者100例及混合型患者10例。患者Ki-67数值为3%~88%,平均为69%,其中Ki-67数值≥80%患者40例;骨髓涂片显示,骨髓侵犯患者210例,两种检查方式结果统计后,245例患者骨髓侵犯,两种检查方式用于DLBCL骨髓浸润诊断的一致性良好(Kappa=0.905);DLBCL细胞大小适中,细胞核呈圆形或不规则型,染色质颜色表现为深紫红色,核仁数量大多为1~5个;胞浆为蓝色。结论DLBCL骨髓侵犯诊断中骨髓涂片形态检查可作为有效方法,当有核细胞中不典型淋巴细胞占比超过1%,则需进一步诊断是否发生骨髓侵犯。

存活蛋白和P63蛋白在B细胞非霍奇金淋巴瘤组织中的表达及其对细胞凋亡和增殖的作用

本研究探讨存活蛋白(Survivin)和P63蛋白在B细胞非霍奇金淋巴瘤(B-NHL)发生发展中的可能作用及其与细胞凋亡和增殖的相互关系。应用免疫组织化学SP法和TdT介导的dUTP缺口末端标记(TUNEL)技术检测43例B-NHL和10例反应性增殖淋巴组织(RHL)中的survivin和P63蛋白表达以及细胞凋亡和增殖细胞核抗原(PCNA)的水平。结果表明:survivin和P63在43例B-NHL中表达的阳性率分别为69.8%(30/43)和82.7%(36/43),survivin和P63在10例RHL中表达阳性率分别为10%(1/10)和40%(4/10),survivin在侵袭性B-NHL中的阳性率明显高于惰性B-NHL(83.3%vs46.2%,P<0.01),P63蛋白表达差异无显著性意义;survivin阳性表达与凋亡指数(AI)和增殖指数(PI)呈正相关(r=0.429,P<0.01;r=0.348,P<0.01),P63蛋白阳性表达与AI和PI呈正相关(r=0.451,P<0.01;r=0.369,P<0.05),B-NHL的AI和PI呈显著正相关(r=0.598,P<0.001)。结论:survivin可能参与了B-NHL的凋亡和增殖调控机制,P63作为癌基因参与B-NHL发生,二者可能共同影响细胞增殖和凋亡。

侵袭性B细胞淋巴瘤中PIK3CA扩增和PTEN缺失及其临床病理学意义

目的:探讨侵袭性B细胞淋巴瘤在PI3K/Akt/mTOR信号通路中PIK3CA与10号染色体上缺失的磷酸酶和张力蛋白同源物(phosphate and tension homology deleted on chromsome ten,PTEN)的表达情况及其与各临床病理指标的相关性。方法:回顾性分析新疆医科大学第一附属医院2008年1月至2012年12月术前未经任何治疗的侵袭性B细胞淋巴瘤标本235例,其中包括弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)205例,伯基特淋巴瘤(Burkitt lymphoma,BL)27例,灰区淋巴瘤(介于DLBCL和BL之间,不能分类的B细胞淋巴瘤)3例。应用荧光原位杂交技术检测所有样本PIK3CA和PTEN基因的表达情况,统计分析其与各临床病理指标及预后的关系。结果:PIK3CA在侵袭性B细胞淋巴瘤中扩增率为12.3%(29/235),临床分期Ⅰ~Ⅱ期和Ⅲ~Ⅳ期的阳性率分别为8.6%(12/139)和17.7%(17/96),差异具有统计学意义(P=0.038)。PTEN在侵袭性B细胞淋巴瘤中的缺失率为13.6%(32/235),与其他临床病理特征无相关性。PIK3CA扩增和PTEN缺失呈负相关(P=0.046)。未发现PIK3CA扩增和PTEN缺失与生存期存在相关性。结论:PIK3CA扩增与侵袭性B细胞淋巴瘤疾病晚期相关,PIK3CA扩增和PTEN缺失在侵袭性B细胞淋巴瘤的发生中起促进作用。