骨髓增生异常综合征T淋巴细胞异常与克隆造血

 目的　了解T淋巴细胞异常在骨髓增生异常综合征（MDS）克隆造血中的作用。方法　对76例MDS患者的染色体核型、T淋巴细胞亚群及激活状态进行分析。结果　正常核型36例,异常核型40例,异常发生率52.6 %。40例异常核型中,三体8（+8）24例,占异常核型的60.0 %。与健康对照组比较,MDS患者CD+3 CD-19、CD+3 CD-4 CD+8以及CD+3 HLA-DR+细胞百分率显著升高,CD-3（CD16 CD56）+细胞的百分率明显降低。将MDS患者进行核型分组,异常核型组CD+3（CD16 CD56）+细胞的百分率显著高于正常对照组。将+8核型从MDS异常核型中独立出来进行分析,CD+3 CD+4 CD-8细胞的百分率明显低于正常核型以及其他异常组,CD4／CD8的比值明显低于健康对照组。结论　MDS存在T淋巴细胞异常,异常核型MDS可能恶性克隆增殖更为优势,预后更差。+8 核型MDS存在更为严重的免疫监视功能下降,导致恶性克隆过度增殖与残存造血过度受抑。     

骨髓增生异常综合征的临床特征及T淋巴细胞亚群分析

目的 探讨骨髓增生异常综合征伴多系病态造血(MDS-MLD)外周血常规和骨髓象特点,并分析T淋巴细胞亚群情况,为临床诊疗提供依据.方法 选取中国中医科学院西苑医院2021-01-01-10-30确诊的MDS-MLD患者27例和健康体检者8名,用流式细胞仪检测外周血常规中Th1、Th2、Th17和Treg淋巴细胞比例,采...     

骨髓增生异常综合征患者淋巴细胞亚群特点及环孢素对其的影响

目的 检测和分析骨髓增生异常综合征（MDS）-难治性贫血（RA）及-难治性血细胞减少伴有多系发育异常（RCMD）患者T淋巴细胞亚群的分布,评估MDS患者免疫功能状态及环孢素（CsA）对T淋巴细胞亚群的影响.方法 采用流式细胞术（FCM）对MDS-RA及-RCMD患者和13名健康对照外周血标本进行淋巴细胞亚群检测,检测MDS-RA及-RCMD患者在应用以CsA为基础的免疫抑制方案治疗前、治疗6个月后的淋巴细胞亚群的表达情况.结果 MDS组的Th细胞（CD3＋CD4＋）、Th/Ts（CD1＋CD8＋）比值均低于健康对照组[（35.72±5.02）％比（45.73±2.15）％、（1.89±0.51）％比（2.41±0.39）％],差异有统计学意义（t值分别为13.39、3.64,均P＜0.05）;Ts细胞的表达高于健康对照组[（29.07±3.88）％比（21.80±3.63）％],差异有统计学意义（t=6.47,P＜0.05）;治疗前后Th细胞、Ts细胞、Th/Ts比值差异均有统计学意义（治疗后分别为（38.19±4.98）％、（26.03±3.03）％、（1.96±0.35）％,t值分别为0.39、2.65、3.57,均P＜0.05）.CsA治疗6个月后有效和无效组比较,Th细胞[（42.79±7.74）％与（36.46±1.28）％]、Ts细胞[（22.14±3.91）％与（27.51±2.84）％]、Th/Ts比值[（2.40±0.40）％与（2.08±0.11）％]差异均有统计学意义（t值分别为67.65、3.77、3.57,均P＜0.05）.结论 MDS患者T淋巴细胞亚群免疫失调导致细胞免疫功能紊乱,CsA可改善MDS患者的T淋巴细胞亚群失衡.     

骨髓增生异常综合征的治疗进展

骨髓增生异常综合征是一组造血干细胞克隆性疾病,因病态造血导致进行性、难治性血细胞减少为特征,临床主要表现为贫血、感染和出血。少数有进展为急性白血病的危险。目前仍缺乏有效的根治疗法,本文重点讨论MDS的现有治疗和相关的支持治疗。     

骨髓增生异常综合征的治疗进展

骨髓增生异常综合征是一组造血干细胞克隆性疾病,因病态造血导致进行性、难治性血细胞减少为特征,临床主要表现为贫血、感染和出血。少数有进展为急性白血病的危险。目前仍缺乏有效的根治疗法,本文重点讨论MDS的现有治疗和相关的支持治疗。     

骨髓增生异常综合征的靶向治疗

骨髓增生异常综合征(myelodysplastic syndrone,MDS)是包括一组不同起源的造血干/祖细胞克隆性疾病,以无效造血和向急性白血病转化为特点.MDS的发展虽有近百年的历史,但对MDS的发生机制的认识仍然有限,阻碍了MDS治疗的发展.近年来,MDS发病机制的研究在分子生物学水平有了一些突破,出现了很多的靶点,许多针对这些靶点的新药相继出现并在临床试验中获得了令人鼓舞的成绩.各个试验的疗效标准各不相同,但与2000年国际工作组制定的判定标准基本统一.     

骨髓增生异常综合征的现代治疗

骨髓增生异常综合征（ＭＤＳ）是克隆性造血干细胞疾患,临床表现呈现多样性、异质性,以血细胞减少为其特征。少数有进展为急性白血病的危险。在既往１０年中出现了许多新的治疗,有些新药正在研发之中。本文复习讨论ＭＤＳ的分类和预后系统,重点复习ＭＤＳ的现有治疗和相关的支持治疗。     

低增生性骨髓增生异常综合征治疗的进展

 低增生性骨髓增生异常综合征（Hypo-MDS）骨髓结构紊乱，病态巨核细胞增生明显，以骨髓低细胞容积和病态造血为共同特征，目前尚无统一的治疗标准，对其治疗应该引起注意。文章对Hypo-MDS治疗的研究进展进行了综述。     

Myelodysplastic Syndrome Associated with Bone Marrow Fibrosis

Bone marrow biopsy (BMB) in myelodysplastic syndrome (MDS) frequently reveals a slight alteration in the reticulin stroma which does not have any clinical significance. However, in a minority of cases, full-blown bone marrow fibrosis (BMF) can be found.

Primary MDS patients with BMF show distinct clinico-pathological features and an unfavourable prognosis mainly attributable to complications deriving from pancytopenia and continuous transfusions, while leukemic transformation occurs only rarely. Since BMF may characterize other hematological disorders, primary MDS with BMF should be included in the differential diagnosis particularly with malignant myelofibrosis (MM) and idiopathic myelofibrosis (IMF).

Secondary MDS with BMF represent a variety of preleukemic conditions in subjects treated for previous neoplasias. Unlike the primary forms, they do not form a clearcut clinico-pathological entity.     

骨髓增生异常综合征DNA甲基化及其治疗机制的进展

骨髓增生异常综合征（myelodysp lasticsyndrome,MDS）仍为血液病学较难攻克的一大主题。近年由于DNA甲基化研究的进展及DNA去甲基化药物的开发、使用,为MDS的治疗提供了更多可能的靶点。全文就近年DNA甲基化及去甲基化治疗相关机制的研究进展作一介绍。     

Intravenous Bolus Topotecan in Patients with Myelodysplastic Syndrome

We treated 16 patients with myelodysplastic syndromes with 24 courses of bolus topotecan. Patients received topotecan as a daily 15 minute infusion for 5 days at 3 dose levels (4.0 mg/m²/d, 2.0 mg/m²/d or 2.5 mg/m²/d). There was one complete response and one partial response (overall response rate 12%). Toxicity included myelosuppression, diarrhea, ileus and mucositis. There were 3 treatment-related deaths. The results of this schedule of topotecan appeared to be inferior to that reported with infusional topotecan in patients with MDS.     

Neutrophil to Lymphocyte Ratio - Not an Independent Prognostic Factor in Patients with the Myelodysplastic Syndrome

Purpose: Neutrophil-to-lymphocyte ratio (NLR) was evaluated as a potential prognostic factor in patientswith myelodysplastic syndrome (MDS). Materials and Methods: Between December 2009 and April 2014, 14female (35%) and 26 male (65%) MDS patients who were followed up in our hematology clinic were included inthe study for NLR during diagnosis. Division was into two groups according to the NLR, and the correlation withmortality was evaluated. The prognostic significance of NLR regarding treatment outcome was also evaluatedwith adjustment for known confounding risk factors. Results: The mortality rate of the patient group was55%, and median survival was 18 months. There was no significant correlation between mortality and NLR ata median value of 1.8 (p=0.75). Thrombocytopenia was observed to increase mortality (p=0.027), and there wasa significant correlation between mortality and pancytopenia (p=0.017). Conclusions: This first study of NLRand mortality did not show any significant correlation . In centres with limited access to genetic evaluation forthe presence of pancytopenia and/or thrombocytopenia at the time of diagnosis, a platelet level less than 50×109/lmay be poor prognostic markers in MDS patients.     

垂体瘤转化基因在骨髓增生异常综合征中的表达

[目的]研究垂体瘤转化基因(PTTG)在骨髓增生异常综合征(MDS)患者中的表达,并分析其与MDS的关系.[方法]采用RT-PCR方法检测32例MDS患者及10例正常骨髓单个核细胞(bone marrow mononuclear cell,BMMNC)中PTTG mRNA的表达.[结果]MDS患者PTTG基因的表达(0.2962±0.2093)明显高于正常对照(0.0590±0.0233,P＜0.05);PTTG在RAEB-1的表达(0.4078±0.1876)及RAEB-2组中的表达(0.4213±0.2589)高于RA及RARS(0.1627±0.0860,P＜0.05),在RAEB-1及RAEB-2组中的表达差异无显著意义(P＞0.05).[结论]PTTG基因的过表达可能与MDS的发生发展有关.     

抗p53融合蛋白单克隆抗体的性质鉴定

目的 :研制出能特异与p5 3结合的单克隆抗体 ,使对 p5 3的检测得到更为广泛的应用。 方法 :以原核表达的 p5 3-GST融合蛋白为免疫原 ,常规方法作细胞融合 ,间接酶联免疫吸附试验 (ELISA)双筛和免疫组织化学(IHC)筛选 ,将能稳定分泌抗人p5 3单抗的杂交瘤细胞株的细胞上清 (命名为M12 6 )与常用p5 3进口单抗PAB180 1(ZYMED公司 )作对比实验。结果 :此单抗适用于ELISA、IHC、免疫印迹及免疫沉淀等方面的研究 ,并且在一定程度上优于PAB180 1。结论 :新制备的单抗M12 6可考虑取代进口单抗PAB180 1而用于p5 3的表达及突变研究。     

TP53 Mutations in Myelodysplastic Syndrome

Mutations of the TP53 tumor suppressor gene, contributing to the development and progression of a wide variety of human malignancies, are found in some of the patients with myelodysplastic syndromes (MDS). Previous reports revealed that TP53 mutations were found in 0-25% of patients with MDS and are closely associated with a complex abnormal karyotype including such chromosomal losses as -5/5q-, -7/7q- and/or 17p-, which are known to be frequent in therapy-related leukemias. We have also detected TP53 mutation in 10 (14%) of 70 patients with MDS. All of the mutations were detected at the time of diagnosis, which suggest the TP53 mutation may play a role in the development of MDS. Those patients with a TP53 mutation had a poor prognosis regardless of leukemic transformation or not.

The reported mutational spectra of TP53 in MDS and ANLL differ from those of colon and lung cancers. Compared with other hematological disorders, the spectrum of TP53 mutations in MDS and ANLL is assumed to be associated with pathogenic exposure to known or unknown carcinogens, as suggested by the chromosomal findings. Further studies are required to clarify the pathogenesis of this heterogenous disease entity.     

高危骨髓增生异常综合征的治疗

骨髓增生异常综合征（MDS）是一类造血干细胞恶性克隆性疾病,其治疗主要集中在表观遗传学治疗、化疗、干细胞移植以及新药方面,现将各种治疗方法进行综述。     

Lymphocyte subsets in patients with brain tumors

Summary T lymphocyte subsets of peripheral blood were studied in preoperative patients with various types of intracranial neoplasms. The subsets were analysed using monoclonal antibodies against lymphocyte membrane markers, and flow cytometry was used to quantitate percent positive cells with the antibodies. Twenty-seven patients were selected for this study, including twelve patients with malignant primary intrinsic tumors histologically consistent with a diagnosis of malignant astrocytoma or glioblastoma multiforme, and fifteen patients with extrinsic tumors diagnosed as meningioma, pituitary adenoma, craniopharygnioma and neurinoma. Twenty-five age and sex-matched individuals without evidence of either local or systemic disorders served as control subjects.The results revealed that the OKT4/8 cell ratio was 1.4±0.4 in the malignant group, 1.8±0.4 in the benign group and 2.1±0.8 in the control group. The ratio was significantly lower in the malignant group than in the control group (p<0.05). Leu-11⁺ cells were found to be 9.7±4.7 in the malignant group, 9.0±3.4 in the benign and 7.8±2.7 in the control group. These results showed that Leu-11⁺ cells in the patients with malignant tumors were significantly increased in comparison with the control group (p < 0.05). The alteration of the lymphocyte subsets is considered to be an effect of neurohormones in balance through the transmission function of the brain-endocrine axis to lymphocytes in immunomodulation.     

单克隆抗体--抗肿瘤药物研究的聚焦点

单克隆抗体作为抗癌药物研究已取得重要进展，人源化抗体技术的成熟，为单克隆抗体抗癌药物在临床上应用奠定了基础。单克隆抗体再次成为抗肿瘤药物研究的聚焦点，并且展现了良好诱人的市场前景。我国在抗肿瘤单克隆抗体研发方面也取得了重大进展．