The single nucleotide polymorphism and haplotype analysis of MDR1 in Jiangsu Han population of China

The aim of this study was to perform the frequency distribution of MDR1 gene SNPs and haplotypes of Jiangsu Han population in China. A total of 225 Jiangsu Han unrelated volunteers were enrolled and genotyped by PCR-ASP method at three loci: C1236 T (rs1128503), G2677 T/A (rs2032582) and C3435 T (rs1045642). In total, C and T were found at locus 1236, with the frequency of 35% and 65%, respectively. The most frequent allele at locus 2677 was G with the frequency of 44%, followed by T (41%) and A (15%). At locus 3435, C was more common (60%) than T (40%). The most common haplotype at loci 1236-2677-3435 was T-T-T (31.84%), at loci 1236-2677 was T-T (37.68%), at loci 2677-3435 was G-C (39.06%), and at loci 1236-3435 was T-T (34.28%). The haplotype linkage disequilibrium study found that all three loci were in linkage disequilibrium, such as T-T at loci 1236-2677, T-T at loci 2677-3435 and C-C at loci 1236-3435 (P < 0.01). The dendrogram study indicated that the distribution of MDR1 SNPs in Jiangsu Han population were close to Japan and Malay populations and far away from European countries. These findings could shade new lights in population genetics and anthropology studies of Han-Chinese. It also provides basic data for research on MDR1 gene polymorphism, disease association and drug resistance study.     

Pegfilgrastim as hematopoietic support for dose-dense chemoimmunotherapy with R-CHOP-14 as first-line therapy in elderly patients with diffuse large B cell lymphoma

Goals of work Recently, 6 cycles of R-CHOP-14 have been recommended as the reference standard regimen for the treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL). Pegfilgrastim has been shown to facilitate dose-dense chemotherapy schedules with a single administration per chemotherapy cycle. The aims of this study were to evaluate the use of pegfilgrastim in combination with the R-CHOP-14 regimen in a homogenous group of previously untreated elderly patients with DLBCL and to assess the pharmacokinetics of pegfilgrastim within this patient population. Materials and methods Ten patients with DLBCL between 60 and 80 years of age received a single subcutaneous injection of 6 mg pegfilgrastim 24 h after administration of R-CHOP chemoimmunotherapy, which was repeated for 6 to 8 cycles in two-weekly intervals. A total of 348 blood samples were collected. Pegfilgrastim plasma levels and absolute neutrophil counts were measured every other day during the first treatment cycle and twice weekly during all consecutive cycles. Main results Sixty-three of 72 cycles (87.5%) could be delivered on time and at the planned dose. Median absolute neutrophil nadir was 0.32 g/l on day 9. Grade 3/4 granulocytopenia occurred in all patients. Febrile neutropenia occurred in two patients. Plasma levels of pegfilgrastim remained elevated during the neutropenic phase. At the start of hematologic recovery, plasma concentrations of pegfilgrastim decreased rapidly to baseline levels. Median pegfilgrastim trough plasma level was 0.43 ng/ml on the day preceding the next application. Conclusions A single fixed dose of 6 mg of pegfilgrastim given once per cycle of R-CHOP-14 is effective in supporting neutrophil recovery to allow two-weekly drug administration in previously untreated elderly patients with DLBCL. However, close monitoring for infectious complications is mandatory in this patient population.     

Advances in the molecular diagnosis of diffuse large B-cell lymphoma in the era of precision medicine

Introduction: The adoption of high-throughput technologies has led to a transformation in our ability to classify diffuse large B-cell lymphoma (DLBCL) into unique molecular subtypes. In parallel, the expansion of agents targeting key genetic and gene expression signatures has led to an unprecedented opportunity to personalize cancer therapies, paving the way for precision medicine.

Areas covered: This review summarizes the key molecular subtypes of DLBCL and outlines the novel technology platforms in development to discriminate clinically relevant subtypes.

Expert commentary: The application of emerging diagnostic tests into routine clinical practise is gaining momentum following the demonstration of subtype specific activity by novel agents. Co-ordinated efforts are required to ensure that these state of the art technologies provide reliable and clinically meaningful results accessible to the wider haematology community.     

鼻腔鼻窦NK/T细胞淋巴瘤与弥漫大B细胞淋巴瘤的临床表现及影像学特征比较

目的比较NK/T细胞淋巴瘤（NKTCL）与弥漫大B细胞淋巴瘤（DLBCL）的临床及影像学特征,以提高其诊断的准确性。方法回顾性收集我院病理证实的鼻腔鼻窦非霍奇金淋巴瘤（NHL）患者的临床及影像学资料,包括15例NKTCL及9例DLBCL,比较两组患者年龄、性别比例、临床症状、病变位置、病灶大小及形态、信号强度、强化程度及均匀性、邻近结构的变化。结果DLBCL患者发病年龄较NKTCL大（P=0.001）,性别差异无统计学意义（P=0.351）;NKTCL患者临床症状以鼻塞多见（93.3%）,DLBCL患者以眼部症状多见（55.5%）。NKTCL多见于鼻腔、DLBCL多见于鼻窦（P < 0.001）;NKTCL病变以弥漫浸润型较多见、DLBCL以肿块型较多见,但两组差异无统计学意义（P=0.099）;DLBCL病灶比NKTCL大（P=0.019）;两组病灶T1WI、T2WI信号及强化程度差异无统计学意义（P > 0.05）;NKTCL病灶多强化不均匀,DLBCL多强化均匀（P=0.009）;NKTCL以鼻背部软组织受累多见（70.0%）,DLBCL以累及眼眶多见（62.5%）;DLBCL较NKTCL对邻近骨质的破坏明显。结论鼻腔鼻窦NKTCL与DLBCL的临床及影像学特征对病理分型有一定的提示作用。NKTCL患者症状主要为鼻塞,影像学上病灶多位于鼻腔、体积较小、强化不均匀、周围骨质毛糙呈轻微骨质破坏;DLBCL患者多表现为突眼、溢泪,影像学上病灶多位于鼻窦、体积大、强化均匀、周围骨质虫蚀样或溶骨样破坏。     

弥漫性大B细胞淋巴瘤中miR-34a、FOXP1表达的相关性及临床意义

目的 研究弥漫性大B细胞淋巴瘤(DLBCL)中微小RNA(miR)-34a、叉头框蛋白P1(FOXP1)表达的相关性及临床意义.方法 选择2018年2月至2019年7月期间经达州市中心医院病理确诊的DLBCL组织79例和反应性增生淋巴结组织60例,采用荧光定量PCR检测miR-34a的表达水平、western blot...     

c-FLIP does not correlate with response to immunochemotherapy treatment and outcome of patients with nodal diffuse large B-cell lymphoma

Cellular FLICE-inhibitory protein (c-FLIP) is a critical anti-apoptotic regulator that inhibits apoptosis-inducing ligand, (TRAIL)-induced apoptosis as well as chemotherapy-triggered apoptosis in malignant cells. The present study was designed to investigate the clinical and prognostic significance of c-FLIP expression in patients with nodal diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy.     

原发性皮肤弥漫性大B细胞性淋巴瘤(腿型)17例临床病理分析

目的探讨原发性皮肤弥漫性大B细胞性淋巴瘤(腿型)(PCDLBCLLT)的临床病理特点。方法回顾性分析17例PCDLBCLLT的临床资料、组织学形态和免疫组化标记。结果 17例PCDLBCLLT的发病年龄为31～86岁,平均64.4岁;其中男性9例,女性8例,男女之比为1.1∶1;主要发生于腿部和躯干部。组织学表现为弥漫分布的肿瘤细胞,以中心母细胞和免疫母细胞为主,核分裂象易见,肿瘤组织不累及表皮。免疫组化:肿瘤细胞表达B细胞相关抗原,bcl-2、MUM1、FOX-P1和bcl-6(+),Ki-67增殖指数为60%～90%。结论 PCDLBCLLT是一种独特类型的大B细胞性淋巴瘤,预后较差。     

弥漫大 B 细胞性淋巴瘤中 bc1-6基因异常及其临床应用价值

目的:观察中国人弥漫大 B 细胞性淋巴瘤(DLBCL)中 bcl-6基因突变、基因重排及蛋白表达的特征,探讨其存 DLBCL 发生中的作用及其临床应用价值。方法:应用聚合酶链反应(PCR)、直接测序和免疫组织化学法分析51例淋巴结内外 DLBCL 和10例淋巴结反应性增生(RLH)石蜡切片组织中 bcl-6基因5’非编码区突变高频区段E1.7、E1.8、E1.10、E1.11、E1.12的突变和蛋白表达;应用荧光原位杂交(FISH)技术检测32例淋巴结内 DLBCL 和5例 RLH 中 bcl-6基因的重排。结果:①12/51(23.5%)DLBCL 存在 bcl-6基因5’非编码区突变.主要集中于 E1.11、E1.12和 E1.10,2/10(20.0%)RLH 的生发中心细胞亦可见有 bcl-6突变;②9/32(28.1%)DLBCL 有 bcl-6基因重排,而 RLH 中均未检测到 bcl-6基因重排;③38/51 (74.5%)DLBCL 中可见 bcl-6蛋白细胞核表达,表达形式有滤泡样型、中间型、散在型,RLH 中可见生发中心细胞均呈 bcl-6阳性表达;④bcl-6基因5’非编码区突变、重排和蛋白表达之间均无显著性相关(P>0.05)。结论:①bcl-6基因突变和蛋白表达均可同时发生于 DLBCL 和 RLH 的生发中心,表明两者是生发中心和生发中心细胞起源 DLBCL 的标志,可用于诊断和鉴别诊断:②bcl-6蛋白在不同病例中的不同表达形式不仅反映了 DLBCL 的异质性,还可能与 DLBCL 的分子亚型和预后有关:③bcl-6基因重排仅发生于 DLBCL而不发生于 RLH,表明其可能参与了部分 DLBCL 的发生,并可作为 DLBCL 诊断的参考指标。     

现实暴露疗法对弥漫性大B细胞淋巴瘤化疗患者心理状况的影响

目的 探究现实暴露疗法对弥漫性大B细胞淋巴瘤化疗患者心理状况的影响.方法 选择2017年6月—2020年6月收治的弥漫性大B细胞淋巴瘤化疗患者120例为研究对象,按性别、年龄、TNM分期有可比性的原则分为对照组和观察组,各60例,对照组采取常规护理,观察组在对照组基础上采用现实暴露疗法,比较两组心理弹性水平、焦虑抑郁状...     

Impact of C-reactive protein and albumin levels on short,medium, and long term mortality in patients with diffuse large B-cell lymphoma

Objectives and study design: In this population-based study of 602 patients, we amended C-reactive protein (CRP) and plasma albumin (PA) levels around the diagnosis of diffuse large B-cell lymphoma (DLBCL) to the International Prognostic Index (IPI) and assessed 0–90, 91–365, and +365-day survival.Results: The CRP did not contribute to the IPI''s prognostic or discriminatory ability, regardless of time period, particularly not in models with PA. In contrast, the PA was an important contributor, especially in the 0–90 day period, but also up to one year after the diagnosis. For day 0–90, the model with the IPI only had an Area Under the Receiver Operating Characteristics (AUROC) of 0.742, whereas the IPI with PA as a continuous variable rendered an AUROC of 0.841. Especially the lower PA quartile (18–32 g/L) contributed to the worse prognosis.Conclusions: The amendment of PA to the IPI may significantly improve the short-term prognostic and discriminative ability.

Key messages

• The amendment of the plasma albumin (PA) level to the International Prognostic Index significantly improved the prediction of mortality up to one year after the diagnosis of diffuse large B-cell lymphoma.
• It was especially the lower quartile of the PA level (18–32 g/L) that contributed to the worse prognosis.

     

弥漫大B细胞性淋巴瘤中bcl-6基因异常及其临床应用价值

目的：观察中国人弥漫大B细胞性淋巴瘤（DLBCL）中bel-6基因突变、基因重排及蛋白表达的特征，探讨其在DLBCL发生中的作用及其临床应用价值。方法：应用聚合酶链反应（PCR）、直接测序和免疫组织化学法分析51例淋巴结内外DLBCL和10例淋巴结反应性增生（RLH）石蜡切片组织中bel-6基因5’非编码区突变高频区段E1．7、E1．8、E1．10、E1．11、E1．12的突变和蛋白表达；应用荧光原位杂交（FISH）技术检测32例淋巴结内DLBCL和5例RLH中bcl-6基因的重排。结果：①12／51（23．5％）DLBCL存在bel-6基因5’非编码区突变，主要集中于E1．11、E1．12和E1．10．2／10（20．0％）RLH的生发中心细胞亦可见有bcl-6突变；②9／32（28．1％）DLBCL有bel-6基因重排，而RLH中均未检测到bcl-6基因重排；③38／51（74．5％）DLBCL中可见bcl-6蛋白细胞核表达，表达形式有滤泡样型、中间型、散在型，RLH中可见生发中心细胞均呈bcl-6阳性表达；④bel-6基因5’非编码区突变、重排和蛋白表达之间均无显著性相关（P〉0．05）。结论：①bel-6基因突变和蛋白表达均可同时发生于DLBCL和RLH的生发中心，表明两者是生发中心和生发中心细胞起源DLBCL的标志，可用于诊断和鉴别诊断；②bcl-6蛋白在不同病例中的不同表达形式不仅反映了DLBCL的异质性，还可能与DLBCL的分子亚型和预后有关；③bcl-6基因重排仅发生于DLBCL而不发生于RLH，表明其可能参与了部分DLBCL的发生，并可作为DLBCL诊断的参考指标。     

^18F-FDG PET/CT在原发性胃弥漫大B细胞淋巴瘤诊断与鉴别诊断中的价值

目的分析原发性胃弥漫大B细胞淋巴瘤（PGDLBCL）的18F-FDG PET/CT影像学特点,探讨其在PGDLBCL的诊断和鉴别诊断价值。方法回顾性分析22例经病理证实的PGDLBCL患者的18F-FDG PET/CT资料,观察病变的部位、范围、最大厚度（THKmax）、CT值、最大标准摄取值（SUVmax）及淋巴结受累情况。将正常胃和进展期胃癌（AGC）患者各30例作为对照。采用统计学分析3组病例之间的可能差异。结果 PGDLBCL的PET/CT表现以不同形式及程度的胃壁增厚和显著增高的18 F-FDG代谢为主要特征。16例（72.73%）为弥漫性增厚,5例（22.73%）为节段性增厚,1例（4.55%）为局限性增厚。THKmax值为（2.74±1.40）cm。CT平扫密度均匀,CT值为（36.82±2.83）HU;SUVmax值为（19.96±5.47）。13例（59.09%）伴有多个区域淋巴结转移。与AGC相比,弥漫性增厚、局限性增厚、SUVmax值（9.35±4.42）及多区域淋巴结转移发生率等征象差异均有统计学意义（均P〈0.05）;而节段性增厚（8,26.67%）、THKmax值（2.38±1.27cm）及CT值（35.20±5.41HU）等征象差异均无统计学意义（均P〉0.05）。结论 18 F-FDG PET/CT有助于全面反映PGDLBCL的病理学、生物学特性,在诊断及鉴别诊断中具有较高的临床价值。     

肝血管内大B细胞性淋巴瘤2例临床病理观察

目的探讨肝血管内大B细胞性淋巴瘤的临床病理特征、诊断与鉴别诊断、治疗及预后。方法回顾性分析2例肝血管内大B细胞性淋巴瘤患者的临床资料、组织病理学形态和免疫组化结果。结果光镜下肝窦内和小血管内可见较多具有明显异型性的淋巴样细胞浸润,汇管区可见慢性炎细胞浸润,亦可见少许异型淋巴细胞样细胞,未见明确纤维化。免疫组化示CD20、PAX5弥漫(+),CD3散在少许(+),Ki-67阳性率为70%,AE1/AE3、CD117和CD56均(-);其中例1 CD5弥漫(+)。结论血管内大B细胞性淋巴瘤是一种具有高度侵袭性的结外弥漫性大B细胞性淋巴瘤的亚型,由于该病临床表现多样及不典型性,造成了部分患者的诊断困难,因此,掌握临床病理及免疫组化特征对该病的诊断和鉴别诊断具有重要意义。     

Long noncoding RNA HULC predicts poor clinical outcome and represents pro-oncogenic activity in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel prognostic markers and therapeutic targets of DLBCL. Emerging studies have implicated that long noncoding RNAs (lncRNAs) are differentially expressed in various tumors and play an important role in the development of cancer. Previously, our group has reported that the novel lncRNA HULC has important biological function and clinical potential in human pancreatic cancer. Here, we investigated the expression of HULC in a cohort of DLBCL to assess its expression pattern, clinical value and molecular mechanism. Firstly, we found that HULC was remarkably overexpressed in both DLBCL tissues and cell lines. Moreover, we illustrated that HULC was closely related to DLBCL characteristics, such as Ann Arbor stages, B symptoms, CHOP-like treatment, rituximab and IPI. Importantly, we verified that HULC was an key predictive factor for DLBCL diagnosis and prognosis from sizable samples through the long time follow-ups. Furthermore, we reveal that the HULC knockdown could significantly arrest cell proliferation and induce apoptosis by repressing cyclin D1 and Bcl-2 in DLBCL cells. Our results suggested that HULC could represent a novel indicator of poor prognosis and may be served as a potential target for the diagnosis and gene therapy of DLBCL.     

梭形细胞变异型非特指性弥漫性大B细胞性淋巴瘤2例临床病理观察

目的 探讨梭形细胞变异型非特指性弥漫性大B细胞性淋巴瘤(DLBCL)的临床病理特点及鉴别诊断.方法 对2例梭形细胞变异型非特指性DLBCL进行组织形态学观察及免疫组化、原位杂交、基因重排检测并文献复习.结果 2例均为女性,年龄分别为15岁和22岁.例1发生于腹腔肠系膜及大网膜,例2发生于前上纵隔.镜下肿瘤细胞肉瘤样生长,交错呈束状排列,间质有明显胶原纤维;肿瘤细胞胞质较少,核呈梭形或卵圆形,染色质粗颗粒状.免疫组化显示肿瘤细胞vimentin、CD45、CD20、CD79a、Pax5和MUM-1弥漫(+),例1 CD5(+),例2CD5(-),而其他抗体2例均(-).IgH基因重排可见较强克隆性重排条带.结论 梭形细胞变异型非特指性DLBCL非常罕见,需要与多种梭形细胞肿瘤鉴别.准确的诊断需要病理形态学观察与免疫组化和基因重排检测相结合,治疗以放、化疗为主,预后较好.     

弥漫大B细胞淋巴瘤患者TLR4、NF-κB蛋白的表达及临床意义

目的探讨弥漫大B细胞淋巴瘤(DLBCL)患者Toll样受体4(TLR4)、核因子κB(NF-κB)蛋白的表达及临床意义。方法选取2015年4月至2017年1月该院诊治的118例DLBCL患者作为观察组,118例体检健康者作为健康对照组,对比2组研究对象TLR4、NF-κB蛋白的表达水平及与不同病理学特征的关系,并分析与DLBCL患者预后的关系。结果观察组的TLR4、NF-κB蛋白阳性表达率明显高于健康对照组(P<0.05);DLBCL患者的临床分期、乳酸脱氢酶(LDH)及国际预后指数(IPI)与TLR4及NF-κB蛋白阳性表达率有关(P<0.05),年龄、性别、结外累及、B症状等指标均与TLR4、NF-κB蛋白阳性表达率无关(P>0.05);TLR4、NF-κB蛋白表达为阳性的患者生存率显著低于阴性表达的患者(P<0.05)。结论TLR4及NF-κB蛋白在DLBCL患者中高表达,且与DLBCL患者的临床分期、LDH及IPI相关,可作为DLBCL发展及预后的评定指标之一。     

免疫化疗对弥漫性大B细胞淋巴瘤患者预后评价因子的影响

目前联合利妥昔单克隆抗体的免疫化疗已成为弥漫性大B细胞淋巴瘤(DLBCL)的一线治疗方案。本研究借助当前免疫化疗状况对过去国际预后指数(IPI)及目前报道的几种不同免疫学亚型的预后指导价值进行评估分析。采用回顾性分析方法,分别收集接受免疫化疗的病例(R-CHOP组,51例)和常规化疗的病例(CHOP组,75例)的临床资料,并通过免疫组织化学方法,按目前报道的常用分型方法将两组患者分成不同的免疫学亚型,并探讨两组间不同临床因素、IPI分组及不同免疫学亚型分型对治疗反应率和预后的提示作用。结果表明,CHOP组75例。R-CHOP组的治疗完全反应率(68.6%)明显高于CHOP组(58.7%),年龄因素和IPI风险评分在两组中都有提示预后的作用。Han模型及Muris模型区分不同的免疫学亚型,结果在CHOP组有一定的治疗反应率和预后提示作用,而在R-CHOP组,不同的免疫学亚型间没有明显的治疗反应率和预后差异。结论:IPI评分在免疫化疗中仍具有重要的预后评价作用,但利妥昔单克隆抗体的应用可能会使基因学差异导致的预后影响减弱甚至消失。免疫化疗的应用提高了DLBCL的治疗反应率及生存率。     

CARMA1基因在活化B细胞样亚型弥漫大B细胞淋巴瘤中的研究进展

弥漫大B细胞淋巴瘤(DLBCL)为常见的侵袭性淋巴瘤,其中活化B细胞样(ABC)亚型DLBCL患者复发率高、生存率低,预后差.核因子(NF)-κB信号通路持续过度活化,是区分ABC亚型DLBCL与其他亚型DLBCL的显著特征之一,亦为导致ABC亚型DLBCL疾病发生的关键信号通路.近年,多项研究结果证实CARMA1通过调控NF-κB信号通路,进而在ABC亚型DLBCL疾病发生中发挥重要作用.笔者拟就CARMA1功能、基因点突变及翻译后修饰等方面对ABC亚型DLBCL疾病发生的影响进行综述.