谷胱甘肽S-转移酶P1基因多态性与儿童支气管哮喘易感性

目的探讨谷胱甘肽S-转移酶P1（GSTP1）基因多态性与儿童哮喘易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析检测51例哮喘患儿（病例组）和40例正常儿童（对照组）GSTP1 Ile105/Ile105、Ile105/Val105和Val105/Val105三种基因型分布频率。结果GSTP1基因的Ile/Ile、Ile/Val、Val/Val基因型分布频率在病例组分别为66.7%、27.4%、5.9%,Ile和Val等位基因的分布频率为80.4%、19.6%;而对照组Ile/Ile、Ile/Val、Val/Val基因型分布频率分别为90.0%、7.5%、2.5%,Ile和Val等位基因的分布频率为93.8%、6.2%。二组GSTP1基因型的分布频率差异显著（χ^2=6.947 P〈0.05）。病例组Ile/Val和Val/Val基因型占优势（OR=4.5,95%可信区间1.375-14.729）。二组GSTP1基因Ile和Val等位基因的分布频率差异显著（χ^2=6.751 P〈0.05）,病例组Val等位基因的分布频率高于对照组。结论GSTP1 Ile/Val、Val/Val基因型与哮喘存在相关性,Val等位基因与哮喘易感性有关,提示GSTP1基因多态性可能在哮喘遗传易感性方面有重要作用。     

谷胱甘肽巯基转移酶基因型与儿童急性淋巴细胞白血病化疗相关毒副反应的关系

目的探讨谷胱甘肽巯基转移酶(GST)基因型与儿童急性淋巴细胞白血病(ALL)化疗相关毒副反应的关系。方法随机抽取2003年1月-2008年12月间在复旦大学附属儿科医院血液肿瘤科接受化疗的80例ALL患儿,应用PCR方法进行GSTT1和GSTM1基因型检测,分析GST基因型与诱导化疗和大剂量甲氨蝶呤(HD-MTX)化疗相关毒副反应的关系。结果检出GSTT1缺失基因型11例(13.8%),GSTM1缺失基因型27例(33.8%)。诱导化疗期中高危组GSTM1缺失基因型患儿肝损害发生率显著高于GSTM1非缺失基因型患儿(53.3%vs10.3%,P=0.011)。GSTT1和GSTM1基因型与标危组诱导化疗和HD-MTX化疗相关肝损害的发生无关,与化疗相关感染的发生也无关。结论 GSTM1基因型与接受较强烈诱导化疗的ALL中高危组患儿化疗相关肝损害的发生相关。     

巯基嘌呤甲基转移酶遗传多态性与儿童急性淋巴细胞性白血病

６＿巯基嘌呤 (６＿ｍｐ)早在５０年代用于治疗白血病 ,为儿童急性淋巴细胞白血病 (ＡＬＬ)最为广泛应用的药物之一。在标准化疗方案中 ,它作为缓解后维持治疗的主要药物。近几年来 ,随着化疗个体化创见的提出 ,化疗药物基因组学成为研究的焦点。本文就巯基嘌呤甲基转移酶 (ＴＰＭＴ)的遗传多态性与儿童ＡＬＬ的临床相关性作一综述。一、６＿ｍｐ 代谢６＿ｍｐ 和其他巯嘌呤抗代谢药 ,均为无活性的药物前体 ,须经代谢为硫鸟嘌呤核苷酸 (ＴＧＮｓ) ,以发挥其抗肿瘤活性［１］。口服６＿ｍｐ后 ,进一步经胃肠道和肝脏代谢。生物体内存在３条竞…     

儿童传染性单核细胞增多症与急性淋巴细胞白血病GST基因遗传多态性研究

目的：探讨谷胱甘肽硫转移酶基因GSTT1及GSTM1多态性与儿童传染性单核细胞增多症（IM）、儿童急性淋巴细胞白血病（ALL）易感性的关系。方法：采用多重PCR技术对106例IM患儿、41例ALL患儿和100例非血液系统性疾病、非肿瘤疾病患儿外周血标本进行GSTT1和GSTM1基因多态性检测,分析不同基因型与儿童IM、ALL发病的关系。结果：IM组GSTT1纯合缺失基因型频率明显高于对照组,差异有统计学意义（P<0.05）;携带GSTT1纯合缺失基因型的个体发生IM的风险是携带GSTT1非纯合缺失基因型个体的2.186倍。GSTM1/GSTT1基因联合缺失型个体发生IM的风险是非联合缺失型个体的4.937倍。GSTM1纯合缺失基因型在ALL组的分布频率明显高于对照组,差异有统计学意义(P<0.05)。携带GSTM1纯合缺失基因型的患儿发生ALL的风险是携带GSTM1非纯合缺失基因型个体的2.242倍。GSTM1/GSTT1基因联合缺失型个体发生ALL的风险是非联合缺失型个体的8.552倍。结论：GSTT1或GSTM1纯合缺失基因型的儿童对IM或ALL易感性升高,当同时存在GSTT1和GSTM1纯合缺失时,IM或ALL易感性更高。GSTT1和GSTM1在IM及ALL致病过程中可能都发挥了作用。     

TEL-AML1融合基因与儿童急性淋巴细胞白血病

急性白血病（AL）的病因及发病机制尚未完全阐明,目前发现细胞遗传学改变在白血病发生中起重要作用,约1/3的小儿急性淋巴细胞白血病（ALL）患儿表达染色体易位形成的融合基因,TEL-AML1融合基因是最常见的细胞遗传学异常,占儿童ALL20%-25%。本文对TEL-AML1融合基因结构、致白血病作用及其与儿童ALL的预后关系作一综述。     

CYP3A与MDR1基因多态性在儿童急性淋巴细胞白血病的研究进展

儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)作为一种治愈率较高的疾病,化疗是其主要的治疗方法。CYP3A与MDR1作为决定药物代谢的关键基因,两者参与ALL化疗中大多数药物的代谢;两者基因多态性的表达会影响到药物代谢酶的活性进而影响药物代谢的效率。所以在日益提倡个体化治疗的今天,两者基因多态性的表达就直接关系到儿童ALL的治疗效果、药物毒副作用和预后。我们则可以根据两者基因多态性结合患儿的临床表现及其他实验室检查更为细致的划分出标危、中危和高危,采取不同的化疗方案,为实行个体化治疗提供理论依据。     

IL-15单核苷酸多态性与儿童急性淋巴细胞白血病治疗反应相关性

目的探讨白介素15(IL-15)单核苷酸多态性(SNP)位点与中国儿童急性淋巴细胞白血病(ALL)治疗反应的相关性。方法提取ALL患儿缓解期的骨髓细胞基因组DNA,采用质谱阵列技术(MassArray)分析IL-15的5个SNP位点(rs10519612、rs10519613、rs17007695、rs17015014、rs35964658),并对各SNP位点与诱导治疗结束后微小残留病(MRD)进行相关性分析。结果 SNP rs17007695与儿童ALL早期诱导治疗结束后的MRD相关(P=0.049),CC基因型诱导结束时MRD阳性率是TT基因型的1.8倍;5个SNPs的单倍型分析显示,CACGG在MRD阳性组中出现的频率高于MRD阴性组,差异有统计学意义(10.5%对4.9%,P=0.035)。结论 IL-15相关的SNP与儿童ALL早期治疗反应相关。     

儿童急性淋巴细胞白血病化疗后免疫系统重建的研究

目的 观察急性淋巴细胞白血病(ALL)儿童在化疗结束后淋巴细胞亚群和免疫球蛋白的变化,了解化疗后免疫系统的恢复过程.方法 采用流式细胞仪分析76例ALL治疗后停药患儿的外周血淋巴细胞亚群,应用单向琼脂扩散法测定其中64例患儿血清IgA、IgG、IgM的浓度.结果 CD3 HLA-DR 细胞、CD4 CD45RO-CD45RA-细胞百分率在停药后0～12个月组高于对照组(P<0.05),CD3 CD4-CD8 、CD8 CD28-细胞百分率在停药后0～12个月、12～24个月、24～48个月组均高于对照组,CD3 CD8-CD4 、CD4 CD29-、CD4 D45RO-CD45RA 细胞的百分率、CD4/CD8比值、CD45RA/CD45RO比值在停药各个阶段与对照组相比明显降低(P<0.05).CD19 CD5 细胞的百分率在停药后0～12个月、12～24个月组高于对照组,IgG浓度停药0～12个月低于参考值(P<0.05).结论 化疗结束后,患儿的免疫系统恢复需要较长的时间.NK细胞在停药时即正常.B细胞在停药2年后已经基本恢复,T淋巴细胞的恢复最慢.     

端粒酶活性与儿童急性淋巴细胞白血病相关性的研究

目的了解端粒酶在儿童急性淋巴细胞白血病中的表达情况。方法采用端粒重复序列扩增法（ＴＲＡＰ）检测了１４例儿童急性淋巴细胞白血病骨髓单个核细胞端粒酶活性水平，并与１０例正常健康儿童外周血和骨髓单个核细胞端粒酶活性相比较。结果白血病细胞端粒酶活性显著升高，可高达Ｋ５６２白血病细胞端粒酶活性的７５％～９８％，而正常外周血和骨髓单个核细胞具有适度低水平的酶活性，其相对活性为Ｋ５６２细胞的１．３％～５．７％。结论端粒酶的激活在急性淋巴细胞白血病的发生发展中可能具有重要作用。     

GSTP1 A313G多态性与儿童急性淋巴细胞白血病无关联——基于9篇病例对照研究的Meta分析

目的 对GSTP1 A313G位点AG、GG、AG+GG基因型和G等位基因与儿童急性淋巴细胞白血病（ALL）关联性进行Meta分析。方法 检索PubMed、EMBASE、OVID、中国生物医学文献数据库、中国知网和万方数据库（2000年1月至2014年6月）中的文献,收集GSTP1 A313G多态性与儿童ALL关联性的病例对照研究,应用RevMan 5.3软件和Stata 12.0软件进行Meta分析,统计合并OR值及其95%CI。结果 符合本文Meta分析纳入标准的文献有10篇,其中9篇文献具同质性（病例组1 476例,对照组1 905例）。Meta分析结果显示,GSTP1 A313G位点AG、GG、AG+GG基因型与儿童ALL发病风险无关联（AG基因型：OR=1.07,95%CI：0.93~1.24,P=0.35;GG基因型：OR=1.12,95%CI：0.86~1.45,P=0.41;AG+GG基因型：OR=1.08,95%CI：0.94~1.24,P=0.28）,G等位基因与儿童ALL发病风险亦无关联性（OR=1.11,95%CI：0.96~1.28,P=0.16）。按种族、对照组来源、基因分型方法和样本量大小行分层分析,显示GSTP1 A313G位点上述基因型和等位基因与儿童ALL发病无关联。结论 GSTP1 A313G位点多态性与儿童ALL发病风险无关联。     

儿童淋巴瘤与淋巴细胞性白血病的鉴别诊断与治疗差异

儿童淋巴系统恶性肿瘤主要包括急性淋巴细胞性白血病（ALL）和淋巴瘤。ALL可发生类似淋巴瘤的局部浸润,而淋巴瘤易发生类似ALL样的骨髓转移,因此给临床医师的诊断和治疗造成了一定的难度,现从淋巴细胞的不同发育成熟阶段恶性转化后形成的不同临床类型肿瘤的角度出发,讨论其相应的形态、免疫表型和融合基因特征及二者的鉴别诊断及相应的治疗差异。     

Changes in Lactate Dehydrogenase Isoenzymes Associated with Relapse of Childhood Acute Lymphocytic Leukemia

Twenty-eight children with high-risk acute lymphocytic leukemia underwent monthly serum lactate dehydrogenase (LDH) and WH isoenzyme fraction determinations to examine whether WH isoenzpe fractions change with an increase in the body burden of tumor cells. The 9 patients who relapsed and 5 patients who presented with leukemia during the study period had a slightly lower mean LDH-1 isoenzyme fraction. When the period from 3 months before to 3 months after relapse was examined, significant increases in the LDH-3 isoenzyme fraction and decreases in the LDH-1 and LDH-2 isoenzyme fractions were seen at the time of relapse. These results were highly significant when patients with non-T-cell and T-cell leukemia were combined and when bone marrow and central nervous system relapse was included. The changes at relapse appeared to revert with intensification of chemotherapy. The changes at relapse were not different in magnitude from random variation occurring in patients who remained in remission throughout the study. Although changes in LDH isoenzymes appeared to occur at the time of relapse compared with the periods immediately before and after relapse, these changes were not specific for relapse. LDH isoenzymes do not appear to be useful in predicting relapse in children with leukemia.     

儿童急性淋巴细胞白血病微小残留病与复发的相关分析

目的 分析小儿急性淋巴细胞白血病(急淋)缓解时和缓解不同时期微小残留病(MRD)的水平与复发的相关性。方法：用极限稀释定量PCR法和巢式PCR法追踪检测MRD，数据处理用Kaplan Meier方法及COX回归模型等。结果：46例急淋患儿缓解时MRD值与骨髓复发呈正相关(r=0.4396，P<0.01)，骨髓复发组MRD值为7.359×10-3，与未复发组MRD值(3.954×10-4)差异有显著性(P<0.01)；缓解期MRD持续阳性或由阴性转为阳性者，骨髓复发的相对危险度明显增高(P<0.05)。结论：缓解时MRD水平及缓解期MRD定性结果可作为估计急淋预后的一个重要指标，动态追踪检测MRD是指导治疗和预防复发的有效手段。     

Pseudo-Chediak-Higashi Anomaly in Acute Myeloid Leukemia (M2) of Childhood

The frequency and clinical significance of the pseudo-Chediak-Higashi (PCH) anomaly were studied in 20 children with acute myeloid leukemia (AML) M2 in the FAB nomenclature. PCH granules were recognized as giant eosinophilic granules, measuring up to 5μ, in the cytoplasm of leukemic cells on smears. At the electron microscope level, most PCH granules were round to oval and outlined by a limiting membrane, and contained homogeneous, granular, crystalloid, rod-like or myelin-like materials. The PCH anomaly was demonstrable in five (25.0%) of the 20 patients, which indicates that the anomaly is not rare in childhood AML M2. There were no differences between PCH anomaly-positive and PCH anomaly negative groups with regard to hepatosplenomegaly, hemoglobin levels, white blood cell counts, bone marrow cellularity, t(8q-, 21q+) chromosome abnormalities or prognoses. Circulating leukemic cells were observed less frequently in the PCH anomaly-positive group than in the PCH anomaly-negative group (p <0.05); the leukemic cells were not demonstrable in three of the five patients in the former group, although they were detected in all 15 patients in the latter group. The existence of PCH granules and/or a defect of the cytoskeleton responsible for the PCH anomaly in leukemic cells may impede their movement from the bone marrow to the peripheral blood.     

神经连接蛋白-4基因单核苷酸多态性与孤独症患儿的关系

目的探讨神经连接蛋白-4(NLGN4X)基因单核苷酸多态性(SNPs)与中国汉族儿童孤独症的关系。方法应用聚合酶链式反应与限制性片段长度多态性(PCR-RFLP)分析方法对40例中国汉族孤独症儿童(孤独症组)及40例健康对照儿童(健康对照组)进行2个SNPs位点rs7049300和rs1882260的等位基因和基因型测定。用病例-对照分析SNPs位点等位基因的分布,对孤独症组和健康对照组SNPs位点进行Hardy-Weinberg平衡检验,采用SPSS12.0软件进行统计学分析。结果NLGN4X基因SNPs片段rs7049300和rs1882260的基因型分布频率符合Hardy-Weinberg(χ2=0.008、0.144,Pa>0.05),孤独症组和健康对照组在上述各位点等位基因频率和基因型分布均无统计学差异[rs7049300:χ2(基因型)=1.382,χ2(等位基因)=0.928,Pa>0.05;rs1882260:χ2(基因型)=0.811,χ2(等位基因)=0.921,Pa>0.05]。结论NLGN4X基因上的2个SNPs片段rs7049300和rs1882260与儿童孤独症的发病无关,孤独症的...     

儿童急性髓系白血病的诊断与治疗

近年来,儿童ALL的远期疗效已经得到明显提高,长期无病生存率可达到80%以上.但是儿童急性髓系白血病(AML)的疗效仍不理想.欧美等发达国家推出一系列有效化疗方案.我国专家也结合以往的经验与国际研究进展,提出符合我国国情的儿童AML诊治方案.现结合相关文献资料,将上述国内外经典方案的内容详细列出,并指出各方案的特点与实际疗效,以供读者参考.希望通过努力探索和不断改进,以提高我国儿童AML的远期疗效.     

Chromosome Abnormalities and Prognosis in Childhood Acute Leukemia

We report here on the leukemic cell karyotypes of 134 children with acute nonlymphocytic leukemia (ANLL) examined at Saitama Children's Medical Center (SCMC), and of 88 children with acute lymphoblastic leukemia (ALL) referred to SCMC. The patients were mainly treated according to the protocol of the Tokyo Children's Cancer Study Group. Of 106 ANLL cases with adequate banding, 18% were normal, 34% had miscellaneous clonal abnormalities, and 48% were classified into known cytogenetic subgroups: t(8;21) (n = 21), 11q23 abnormalities (n=14), -7/del(7q) (n = 6), inv (16)/del(16) (n = 5), and t(15;17) (n = 5). According to the FAB classification, M7 (21.7%) were more frequent than in previous reports because this study included a number of Down's Syndrome patients with M7 morphology. The present study confirmed the well-known association of t(15; 17) with M3, t(8;21) with M2, 11q23 abnormalities with M4 and MS, and inv (16)/del(16) with M4. Patients with t(8;21) or inv (16)/del(16q) ANLL fared no better overall than the entire group. Of 51 ALL cases with adequate banding, 13.7% were normal, and 86.3% were classified into abnormal subgroups: translocation (n=14), hyperdiploidy (>50) (n=13), and miscellaneous abnormalities (n = 17). Cases with hyperdiploidy (>50) were restricted to a common phenotype and fared better overall than the entire group. Patients with translocation were found in all phenotypes, and had a poor prognosis. We concluded that childhood acute leukemia could be subgrouped according to karyotypic patterns, and that patients with translocations had a poor prognosis in ALL as well as ANLL.     

儿童急性淋巴细胞白血病的疗效、长期生存与危险因素的关系

目的探讨影响儿童ALL疗效、长期生存与危险因素的关系。方法对采用德国儿童血液、肿瘤协作组ALL治疗方案(COALL-97/GPOH)治疗的50例ALL患儿的临床及实验室资料进行回顾性分析。结果 50例患儿全部完成诱导缓解治疗,完全缓解(CR)率100%。其中随访时间最长者103个月,最短6个月,中位数63个月,复发/死亡14例,无事件生存率(EFS)为64.3%。高危ALL(HR-ALL)19例,标危-ALL(LR-ALL)31例,EFS分别为66.3%和84.8%,其差异有统计学意义(χ2=2.783,P=0.010)。年龄≥10岁18例,<10岁32例,EFS分别为65.3%和82.8%,其差异有统计学意义(χ2=4.662,P<0.01)。初发时外周血白细胞计数≥25×109L-117例,<25×109L-133例,EFS分别为77.9%和82.8%,其差异有统计学意义(χ2=5.581,P<0.01)。B-ALL44例,T-ALL 6例,EFS分别为81.6%和53.3%,其差异有统计学意义(χ2=5.026,P<0.01)。细胞体外药物敏感试验及白血病细胞对泼尼松(PRED)、长春新碱(VCR)及门冬酰胺酶(ASP)的敏感程度积分(PVA-积分)和例数分别为3+4分24例、5-7分15例、8+9分11例,EFS分别为96.1%、79.7%和54.2%,其差异有统计学意义(χ2=3.737,P<0.002;χ2=2.448,P<0.028)。有完整染色体及基因检查资料的患儿27例。其中TEL/WT1(+)5例,死亡1例;BCR/ABL(+)4例,死亡3例;E2A/PBX1(+)并染色体t(1;19)和染色体t(3;7)t(12;22)各1例,2例均死亡。结论年龄、初发时外周血白细胞计数及免疫亚型是评估预后的重要因素;PVA-积分是对ALL临床危险因素分型的补充,使ALL临床分型更细致准确及治疗方案更加个体化。