慢性白血病微卫星不稳定性和杂合性缺失的研究

应用PCR扩增技术检测17例慢性白血病患者不同染色体上8个微卫星位点的微卫星不稳定性（MSI）和杂合性缺失（LOH）,同时检测11例健康志愿者的MSI和LOH,以作对照。结果发现,健康对照组所选微卫星位点均未发生MSI或LOH;9例处于慢性白血病加速期的人中有7例发生至少一个位点的MSI,8例慢性期患者中仅1例发生一个位点的MSI,慢性白血病加速期的MSI发生率明显高于其慢性期（P＜0.05>,提示微卫星的遗传不稳定性可能与慢性白血病的病情进展有关。17例慢性白血病中只有1例在急变后出现LOH,提示所选位点的LOH可能不是慢性白血病的多发事件。     

急性淋巴细胞白血病IgH超基因家族及T细胞受体δ、γ基因的研究

急性淋巴细胞白血病（ＡＬＬ）是一组血液系统的恶性克隆性疾病。目前,尽管应用强效化疗方案及骨髓移植等有效手段,使ＡＬＬ的疗效有较大改观。然而,诱导缓解后的复发问题仍是临床实践中的当务之急,而复发的根源是白血病克隆增殖的结果［１］。本研究以ＩｇＨ、Ｔ细胞受体（ＴＣＲ）γ和ＴＣＲδ基因重排为标志分子,用ＰＣＲ方法检测缓解后微小残留病（ＭＲＤ）,并探讨ＩｇＨ、ＴＣＲδ、γ基因重排在白血病免疫分型中的价值。 一、资料与方法 １．病例：３８例ＡＬＬ患者为初治的住院及门诊患者。全部患者均经临床、细胞形态学以及细…     

急性白血病治疗进展：急性髓细胞白血病的治疗

近年来许多实验资料证明 ,化学药物剂量增加 1倍 ,对白血病细胞杀伤能力增加 10倍。因此 ,国内外不少学者主张对急性白血病患者采用强烈诱导化疗和早期大剂量强化治疗 ,但不等于无限制地盲目地增大剂量和延长用药时间。现将急性髓细胞白血病 (ANLL)的治疗原则总结如下 ,供同道参考。1　诱导缓解目前 ,国内外对急性白血病强烈诱导化疗的方案药物剂量标准不完全一致 ,但一般认为须达到骨髓明显抑制水平 ,外周血白细胞 <1× 10 9/ L,甚至 0 .5×10 9/ L以下。治疗急性 ANL L常用 DA及 HA方案。经过多年来的临床试验后认为 ,目前应用最广…     

急性白血病BCL-2基因的表达及临床意义

目的：探讨急性白血病患者BCL-2基因的表达及临床意义。方法：应用逆转录-聚合酶链反应（RT-PCR）检测40例急性白血病患者细胞中BCL-2基因的表达。结果：BCL-2基因的表达水平与患者的年龄，性别，淋巴结肿大，肝脾肿大，出血，生化乳酸脱氢酶LDH，白血病分型及初治或复发难治等因素无关，但与患者骨髓中原幼细胞数呈正相关，除7例急性早幼粒细胞白血病患者外，BCL-2基因高表达患者完全缓解率（CR）低于低表达者。结论：BCL-2基因的表达对于预测白血病细胞耐药，判断预后，评估化疗反应及选择化疗方案均有十分重要的意义。     

老年急性非淋巴细胞白血病的临床特征

本观察了14例老年急性非淋巴细胞白血病（ANLL)的临床特点，中位年龄70岁，继发于MDS的ANLL 4例，其中仅3例进行2个疗程HOAP方案化疗，完全缓介(CR)只有1例．老年急性白血病患脏器功能减退，常患有多种慢性疾病，对化疗耐受性降低；继发白血病多见，这些可能是导致老年ANLL低缓介率高死亡率的因素。作认为加强支持措施是提高老年ANLL的缓介率．延长缓介期的关键。     

急性白血病p16基因微卫星不稳定性及杂和性缺失的研究

目的分析急性白血病（AL）患者p16基因连锁的微卫星不稳定性（MSI）和杂和性缺失（LOH）,了解p16基因改变与AL发生的关系。方法采用多重PCR方法检测53例AL患者骨髓及口腔黏膜细胞标本的p16基因连锁的3个微卫星位点（D9S162、D9S1748、D9S171）,观察其MSI及LOH情况。结果53例AL患者中,MSI检出率为43．4％（23／53）;位于9p21的p16基因连锁的微卫星D9S162、D9S1748、D9S171的LOH发生率分别为0（0／53）、5．7％（3／53）和9．4％（5／53）,MSI发生率分别为13．2％（7／53）、7．6％（4／53）和7．6％（4／53）。结论AL患者p16基因连锁微卫星均可检测到高频率的MSI和LOH,说明p16基因突变与AL发生、发展有关。     

61例老年人急性白血病临床分析

61例老年人急性白血病临床分析@方炳木$浙江省丽水市中心医院温州医学院附属第五临床医学院血液科!323000 @刘英$浙江省丽水市中心医院温州医学院附属第五临床医学院血液科!323000 @李琳洁$浙江省丽水市中心医院温州医学院附属第五临床医学院血液科!323000 @孙冶$浙江省丽水市中心医院血液病研究室!323000 @刘伟红$浙江省丽水市中心医院温州医学院附属第五临床医学院血液科!323000 @金阳缙$浙江省丽水市中心医院温州医学院附属第五临床医学院血液科!323000 @吴日荷$浙江省丽水市中心医院血液病研究室!323000~~…     

老年期急性非淋巴细胞白血病的治疗

急性白血病,按波及的细胞系列不同,可以分为急性淋巴细胞白血病(简称急淋)与急性非淋巴细胞白血病(简称急非淋).急淋与急非淋都可以发生在儿童期、成人期和老年期(≥60岁).     

MA方案治疗老年急性非淋巴细胞白血病20例疗效观察

自1998年以来，我们使用米托蒽醌加阿糖胞苷(MA)方案作为初治方案治疗老年急性非淋巴细胞白血病患者(ANLL)20例，现报告如下。     

急性淋巴细胞白血病患者治疗前后血清碱性成纤维细胞生长因子水平的检测

血管新生是指在已经存在的血管的基础上以出芽的方式形成新的微血管,存在于很多生理和病理过程中,其与实体瘤的生长、浸润、转移及预后密切相关。PerezAtayde等[1]报道白血病患者骨髓中亦存在血管新生现象,而碱性成纤维细胞生长因子(bFGF)是其中一种重要的促血管新生因子我们采     

The ATM gene and susceptibility to childhood T-cell acute lymphoblastic leukaemia

Ataxia-telangiectasia (A-T) is a multisystem recessive disease characterized by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency and increased risk of cancer. The ATM gene, responsible for A-T, was recently cloned at human chromosome band 11q22-23, a region of frequent alterations in childhood acute lymphoblastic leukaemia (ALL). Children with A-T frequently develop T-ALL. We investigated 18 T-ALL samples for ATM mutations and loss of heterozygosity (LOH) at the ATM locus. No mutations of ATM were found within the coding region in the 18 T-ALL samples, and LOH at the ATM locus was detected in three. The ATM gene appears to be an infrequently altered tumour suppressor gene in childhood T-ALL.     

BRCA2 gene mutation in cancer

Breast cancer susceptibility gene 2 (BRCA2) is the main gene associated with hereditary breast cancers. However, a mutation in BRCA2 has also been found in other tumors, such as ovarian, pancreatic, thyroid, gastric, laryngeal, and prostate cancers. In this review, we discuss the biological functions of BRCA2 and the role of BRCA2 mutations in tumor progression and therapy.     

Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia

Although deletions of cell cycle regulatory gene loci have long been reported in various malignancies, little is known regarding their relevance in pediatric T-cell lymphoblastic lymphoma (T-LBL) and T-cell lymphoblastic leukemia (TALL). The current study focused on loss of heterozygosity (LOH) analyses of the CDKN2A/B (chromosome 9p), ATM (chromosome 11q) and p53 (chromosome 17p) gene loci. Frequencies of LOH were compared in 113 pediatric T-LBL and 125 T-ALL who were treated uniformly according to ALL-BFM strategies. Furthermore, LOH findings were correlated with clinical characteristics and tested for their prognostic relevance. LOH at 9p was detected in 47% of T-LBL and 51% of T-ALL, and was associated with male gender in both. In T-ALL, LOH at 9p was associated with favorable initial treatment response. A tendency for favorable event-free-survival was observed in LOH 9p positive T-LBL. The frequency of LOH at chromosomes 11q and 17p was 5% or less for both diseases.     

Current perspectives on BRCA1- and BRCA2-associated breast cancers

The identification of two breast cancer predisposition genes, BRCA1 and BRCA2, in the mid-1990s has led to a better understanding of the molecular pathogenesis of hereditary breast cancer and to a new era in breast cancer research. The present article reviews the current state of knowledge regarding the biology of BRCA1 and BRCA2, the cancer risks associated with carrying a pathogenic mutation in either of these genes and the possible genetic and environmental risk modifiers. The phenotypes of BRCA1- and BRCA2-associated hereditary breast cancers are reviewed. Research into BRCA1- and BRCA2-associated breast cancer is in its infancy and much remains to be learned, particularly about modifiers of genetic risk and the clinical implications of carrying a mutation in one of these two genes. Australia has an excellent research infrastructure in place, through the Australian Breast Cancer Family Study and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, to contribute substantially to future research in this area.     

The prevalence of BRCA1 and BRCA2 mutations in eastern Chinese women with breast cancer

To investigate the prevalence of BRCA1 and BRCA2 mutations among Chinese patients, we studied 70 Shanghai cases with early onset breast cancer and affected relatives, and mutation screening was performed in the whole-gene sequence of BRCA1 and BRCA2 by polymerase chain reaction-based denaturing high-performance liquid chromatography. Six disease-causing mutations in BRCA1 (8.6%) and two in BRCA2 (2.9%) were detected, including four novel mutations that were all in the BRCA1 gene (3449insA, IVS17-1G>T, IVS21+1G>C and 5587-1del8). Additional sequence variants identified included 30 polymorphisms (18 in BRCA1 and 12 in BRCA2) and a novel mis-sense mutation of unknown significance in BRCA2 (5911G>C). The 9.5 and 2.4% patients with breast cancer diagnosed before the age of 35 were BRCA1- and BRCA2-mutation carriers, and the prevalence of BRCA1 and BRCA2 mutations in the families with two or more affected individuals were 12.1 and 3.0%, respectively. In these families, all the BRCA1 and BRCA2 mutations were detected in the families containing at least one case diagnosed under the age of 40, and in the families whose youngest patients were diagnosed before the age of 35, the prevalence of BRCA1 and BRCA2 were as high as 40 and 20%, respectively. Based on this information, we conclude that genetic testing should be performed among patients with early onset breast cancer (<40 years), especially combined with family history.C-G. Song and Z. Hu contributed equally to the work.     

A bibliometric analysis of the top 100 most cited papers and research trends in breast cancer related BRCA1 and BRCA2 genes

This study aimed to identify, characterize, and map the important attributes of the top 100 most cited papers on BRCA1 and BRCA2 genes. The scientific literature on BRCA1 and BRCA2 was searched in the Web of Science Core Collection database using the keywords “BRCA1” OR “BRCA2” (Title). The top 100 most cited papers were selected based on citations. The obtained data were exported into HistCite^TM, RStudio, and VOSviewer software for prerequisite analysis. The top 100 most cited papers on BRCA1 and BRCA2 were authored by 932 authors from 24 countries and published in 27 journals. These papers were cited 79,713 times, ranging from 441 to 4671 citations. The highly cited paper was cited 4671 times and published in Science (1994). The leading author, journal, publication year, institution, and country were Easton DF (n = 16), Nature Genetics (n = 11), 2002 (n = 11), University of Pennsylvania (n = 17), and the USA (n = 76), respectively. The results show that all the top 100 papers were produced in developed countries. The collaboration index among the authors was 9.49. The most frequently appeared keywords were ovarian-cancer, breast-cancer, mutations, gene, and familial breast. In recent times, the trend topics were patients, mutations, carriers, ovarian, and risk.     

Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families

Purpose: Germline mutations in either BRCA1 or BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancers. At present, over thousand distinct BRCA1 and BRCA2 mutations have been identified. Specific mutations are found to be common within particular populations, resulting from genetic founder effects. To investigate the contribution of germline mutations in these two genes to inherited breast cancer in Iran, we performed BRCA1/BRCA2 mutation analyses in ten Iranian high risk breast cancer families. This is the first study analysing the complete coding sequences of both genes that concerns the Iranian population. Methods: BRCA1/BRCA2 mutation detection included sequencing of the coding and the 3 and 5 untranslated regions. To detect large genomic rearrangements in the BRCA1 gene semi-quantitative multiplex PCR was performed. Results: Two pathogenic mutations in the BRCA2 gene were detected: a novel deletion c.4415_4418delAGAA and a previously described insertion c.6033_6034insGT. In addition, one intronic variation g.5075–53C>T and a deletion/insertion g.*381_389del9ins29 in the 3 untranslated region of BRCA1 were found in two of the investigated families. Both sequence alterations were absent in an age matched Iranian control group. The BRCA2 homozygous variation p.N372H, previously associated with an increased risk for developing breast cancer, was not identified in this study. We did not detect large genomic rearrangements in BRCA1 in patients tested negatively for disease causing mutations in both genes by standard sequencing. Conclusions: At present, the BRCA2 mutations c.4415_4418delAGAA and c.6033_6034insGT have not been identified in any investigated population except the Iranian. Whether both mutations are specific for the Iranian population or a special subgroup remains to be investigated in larger studies. The absence of BRCA1 mutations in the analysed families may suggest that penetrance or prevalence of BRCA1 mutations may be lower in Iran.     

MEIS2、BRCA1表达的相关性及与术后非小细胞肺癌化疗预后的关系

目的探讨非小细胞肺癌(NSCLC)中MEIS2、BRCA1基因表达的相关性及与术后NSCLC化疗预后的关系。 方法收集宜昌市第一人民医院2012年2月至2016年1月住院手术切除并经病理确诊NSCLC的石蜡包埋组织标本61例,收集整理标本对应患者的临床资料,随访患者生存情况。应用免疫组化检测组织中MEIS2及BRCA1基因的表达,分析两者表达的相关性,并将MEIS2、BRCA1表达纳入生存分析,研究两者与NSCLC术后辅助化疗疗效之间的相关性。 结果61例NSCLC患者中,MEIS2和BRCA1的高表达率分别为57.38%(35/61)和65.57%(40/61),两者表达呈正相关(r＝0.59,P＝0.003)。NSCLC患者接受基于铂类药物化疗4～6周期化疗后,20例CR+PR(32.8%),41例SD+PD(67.2%),MEIS2低表达患者有效率为21.3% (13/61),而MEIS2高表达有效率为11.5% (7/61),有极显著性差异(P<0.01);BRCA1低表达患者有效率为23.0% (14/61),而BRCA1高表达有效率为9.8% (6/61),有极显著性差异(P<0.01)。 结论免疫组化显示MEIS2和BRCA1两者的表达存在显著正相关,MEIS2和BRCA1的表达与NSCLC术后接受铂类药物化疗的预后相关,MEIS2和BRCA1表达越低,化疗疗效越好。