慢性淋巴细胞白血病患者脂蛋白酯酶和血清胸苷激酶水平及其与其他预后因素的相关性研究

目的 探讨慢性淋巴细胞白血病(CLL)患者脂蛋白酯酶(LPL)和血清胸苷激酶(TK)水平及其与其他CLL预后因素的相关性.方法 采用RT-PCR方法 检测58例CLL患者外周血标本中LPL的表达水平;增强化学发光法(ECL)和TK1单克隆抗体检测39例CLL患者外周血血清标本中TK1浓度;多重PCR及序列测定检测IgVH基因突变;流式细胞术检测ZAP-70蛋白及CD38的表达;组合探针荧光原位杂交(FISH)技术检测分子遗传学异常.结果 CLL患者LPL中位表达水平为0.26(0～6.29),而在正常对照中均未检测到LPL表达.LPL表达水平与IgVH基因突变、Binet分期、CD38表达和遗传学异常具有显著相关性,无IgVH突变患者的LPL表达水平明显高于突变患者(P=0.010);Binet A期患者LPL表达水平低于Binet B期和C期患者(P=0.011);CD38高表达组(≥30%)LPL表达水平高于CD38低表达组(<30%)(P=0.001);分子遗传学预后较好组[仅有del(13q14)]LPL表达水平明显低于预后较差组[del(17p13)或del(11q22)](P=0.002).LPL表达水平与患者性别、年龄及ZAP-70蛋白表达水平均无明显相关性(P>0.05).CLL患者血清TK1浓度明显高于正常对照(P<0.05).在外周血淋巴细胞绝对计数(ALC)明显增高组(≥50×109/L)、血清乳酸脱氢酶(LDH)高水平组、无IgVH基因突变组和ZAP-70蛋白高表达组(≥20%)的患者中,血清TK1浓度分别明显高于ALC无明显增高组(<50×109/L)(P=0.018)、血清LDH水平正常组(P=0.018)、具有IgVH基因突变组(P=0.030)和ZAP-70蛋白低表达组(<20%)(P=0.038)的患者.血清TK1浓度与CLL患者性别、年龄、Binet分期、CD38表达水平和遗传学异常无明显相关性(P>0.05).结论 CLL患者LPL和血清TK1表达水平与CLL其他预后因素相关,两者均对IgVH突变情况有一定预示作用,在CLL的预后中具有重要价值.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

端粒长度在慢性淋巴细胞白血病中预后意义的初步研究

本研究测定慢性淋巴细胞白血病(CLL)患者端粒相对长度,分析其与年龄、性别、临床分期、ZAP-70蛋白、CD38表达以及免疫球蛋白重链可变区(IgVH)基因突变等临床因素的关系,以初步探讨端粒长度在CLL预后中的意义。选35例外周血或骨髓CLL细胞占80%及以上的CLL患者为研究对象,另选13例正常人作为对照。运用实时荧光定量PCR(qPCR)的方法测定患者及对照者的端粒相对长度,流式细胞术检测患者ZAP-70蛋白及CD38的表达,多重PCR技术测定IgVH基因突变。结果表明:35例患者总平均端粒相对长度为0.384,正常对照为0.443,但两者相比无统计学意义(p0.05)。端粒的长短与CLL分期及IgVH突变状态相关,BinetB、C期患者平均端粒相对长度较BinetA期患者短(p=0.001);IgVH无突变患者较有突变患者平均端粒相对长度短(p=0.015);未发现端粒的长度与患者性别、年龄、ZAP-70蛋白及CD38表达关联(p0.05)。结论:端粒长度可用于CLL的预后判断,结合端粒长度及IgVH突变状态等可以更好地对CLL预后进行分层。     

磷酸二酯酶7B在慢性淋巴细胞白血病患者中的表达及预后意义

目的 为了研究磷酸二酯酶(PDE)7B在慢性淋巴细胞白血病(CLL)患者中的表达及临床意义.方法 应用实时定量逆转录PCR(qRT-PCR)技术检测87例未治疗CLL患者和20例正常人中PDE7B的表达水平,并分析其与CLL临床预后指标的关系.结果 87例CLL患者PDE7B表达水平中位数为5.4×10-4(0.2×1...     

实时定量逆转录PCR检测慢性淋巴细胞白血病中脂蛋白酯酶mRNA的表达及临床意义

目的 研究慢性淋巴细胞白血病(CLL)患者脂蛋白酯酶(LPL)表达情况,探讨LPL在CLL预后中的意义.方法 采用基于Taqman探针技术的实时定量逆转录PCR(qRT-PCR)方法检测62例CLL患者及10名健康对照者外周血标本中LPL的表达水平.对LPL表达水平与免疫球蛋白重链可变区(IgVH)基因突变、ZAP-70蛋白和CD38表达等预后因素进行相关性分析.采用ROC曲线确定LPL表达的最佳分界值,计算其对IgVH突变情况的阳性及阴性预测值.结果 qRT-PCR标准曲线的R2均≥0.990,敏感度可以检测到102拷贝/μg RNA,批内差及批间差变异系数(CV)均小于5%.62例CLL患者LPL表达水平中位数为0.006 0(0～0.737 0).在10名健康对照者中LPL均不表达或低表达,LPL中位表达水平为0(0～0.000 4).在经CD19磁珠分选后的3份CLL患者标本中,LPL相对表达量分别为0.036 0、0.075 0和0.197 0,与分选前表达水平(分别为0.024 0、0.074 0和0.225 0)相似.LPL表达水平与IgVH基因突变情况相关(r=0.45,P<0.05),无突变患者的LPL中位表达水平为0.006 0(0.000 7～0.110 0),明显高于突变患者的LPL中位表达水平[0.002 0(0.000 2～0.027 0)],差异有统计学意义(U=96.5,P<0.05);LPL表达水平与ZAP-70(r=0.38,P<0.05)及CD38(r=0.43,P<0.05)均显著相关.按照IgVH突变情况作为标准对LPL表达水平做ROC曲线分析,确定最佳分界值为0.036 0,敏感度为66.7%,特异度为72.4%,对IgVH突变情况阳性预测值(无突变)为51.8%,阴性预测值(有突变)为83.3%.结论 qRT-PCR方法检测LPL表达敏感可靠.LPL表达水平与CLL重要预后因素IgVH基因突变、ZAP-70、CD38密切相关,并可较准确地预测IgVH突变情况,在CLL的预后中具有重要价值.     

分化抗原簇CD38在慢性淋巴细胞白血病T淋巴细胞中的表达研究

目的 探讨慢性淋巴细胞白血病(CLL)中T淋巴细胞CD38(CD38-T)的表达特征.方法 应用多参数流式细胞术检测83例CLL患者肿瘤细胞中CD38表达(CD38-B)、zeta链相关蛋白-70(ZAP-70)以及CD38-T、CD4/CD8比值的表达情况.结果 在所有患者中,CD38+-T占49.4%(41/83),CD38+-B占50.6%(42/83),CD38+-T和CD38-B表达有高度相关性(r=0.553,P<0.01);表达ZAP-70+CD38+-T和ZAP-70-CD38+-T的患者占67.5%(56/83),CD38-T与ZAP-70的表达有相关性(r=0.349,P<0.01).Binet A期患者中CD38+-T占33.3%(14/42),Binet B+C期患者中CD38+T占65.9%(27/41);XD38+-T与临床分期,CD4/CD8比例倒置有相关性(r=0.312、0.453,P<0.05).结论 CD38-T表达变化与患者病情进展及转归密切相关,CD38高表达的患者多伴有免疫功能调节紊乱或失衡,可作为CLL的一项全新独立的监测指标.     

30例慢性淋巴细胞白血病分子遗传学异常的FISH检测的意义

为探讨间期荧光原位杂交（FISH）在检测慢性淋巴细胞白血病（CLL）＋12、del（13q14）、p53基因缺失、atm基因缺失情况中的意义,采用组合探针（CEP12、LSI D13S319、LSI p53、LSI atm）对30例CLL患者进行FISH检测,分析分子遗传学异常与患者外周血淋巴细胞绝对计数、Binet分期、血清乳酸脱氢酶（LDH）和B：微球蛋白（β2-MG）水平、ZAP-70和CD38表达之间的相关性。结果发现,30例CLL患者中,19例（63．3％）存在1种及1种以上细胞遗传学异常,7例（23．3％）同时检测出2种及2种以上的异常,其中最常见为del（13q14）（43．3％）,其他依次为＋12（23．3％）,atm基因缺失（13．3％）,p53基因缺失（10．0％）。各分子遗传学异常与性别、年龄、Binet分期、外周血淋巴细胞绝对计数、血清LDH和β2-MG水平、ZAP-70表达水平无明显相关性（p〉0．05）,在CD38高表达组中,atm基因缺失的发生率均明显高于CD38低表达组,且差异有统计学意义（p=0．035）。结论：FISH是一种检测CLL患者分子遗传异常快速、准确及敏感的方法,其在CLL患者中的预后预测价值有待进一步的深入研究。     

实时定量逆转录PCR检测慢性淋巴细胞白血病MDM4基因mRNA的表达及其临床意义

本研究旨在探讨慢性淋巴细胞白血病(CLL)患者鼠双微体4(MDM4)基因mRNA的表达情况及其在CLL预后中的意义.采用SYBRGreenⅠ荧光染料行实时定量逆转录PCR(qRT-PCR)方法检测66例CLL患者白血病细胞MDM4 mRNA的表达,以β-actin为内参照物,以2(-△Ct)方法计算MDM4的相对定量值...     

8例Richter综合征临床及生物学特征分析

为了探讨Richter综合征（RS）临床及生物学特征及其预后因素,回顾性分析8例RS患者。利用血清学检测、多参数流式细胞术（FCM）、常规细胞遗传学（CC）、间期荧光原位杂交（FISH）技术、PCR联合DNA序列测定,分别检测患者血清乳酸脱氢酶（LDH）、β2-微球蛋白（β2-MG）、胸苷激酶1（TK1）、血清铁蛋白（SF）和糖链抗原-125（CA-125）,CD38和ZAP-70,染色体核型,ATM和p53基因缺失、＋12异常,以及免疫球蛋白重链可变区（IgVH）突变。结果显示：8例RS患者中7例转化为弥漫大B细胞淋巴瘤（DLBCL）,1例转化为霍奇金淋巴瘤（HL）。7例LDH高于正常值,4例β2-MG高于正常值,7例SF高于正常值,4例CA-125高于正常值,1例TK1高于正常值。4例患者ZAP-70阳性,7例CD38阳性,5例IgVH无突变,4例有染色体复杂核型,1例有＋12,1例有p53缺失。按就诊时BinetA＋B期与BinetC期将患者分为两组,BinetA＋B组从诊断至转化的平均时间为98.5个月,BinetC组为38.3个月,两组间有显著性差异（p=0.021）。平均总生存期（OS）在BinetA＋B组及BinetC组之间分别是123.8个月及49.8个月,两组间有显著性差异（p=0.049）,转化后平均生存时间分别是34.5个月及10.3个月。结论：RS患者血清LDH、β2-MG和SF水平高,ZAP-70和CD38高表达、IgVH无突变发生率高,临床分期可能是RS转化的风险及预后因素。     

慢性淋巴细胞白血病外周血免疫球蛋白异常研究

为了解慢性淋巴细胞白血病（CLL）患者外周血免疫球蛋白（Ig）异常与年龄、性别、疾病分期及预后的关系,运用免疫速率比浊法测定83例CLL患者血清中IgG、IgA和IgM水平,用多参数流式细胞术（FCM）检测患者外周血CD38、ZAP－70表达水平。结果表明：83例CLL患者中IgG减低12例（14．5％）;IgA减低26例（31．3％）,IgM减低34例（41．0％）。BinetC期组Ig减低发生率明显高于BinetA和B期组（P=0．011）,Rai分期高危组的Ig减低发生率明显高于低危组（P=0．011）。Ig减低组CD38和ZAP－70表达阳性率明显较Ig正常组高（P＝0．033和P=0．038）。CD38和ZAP－70在疾病晚期患者表达阳性率更高,其中BinetC期组ZAP－70表达阳性率明显高于BinetA和B期组（P=0．047）。而年龄和性别与Ig异常没有明显相关性（P〉0．05）。结论：CLL患者体液免疫功能与疾病分期密切相关,检测CLL患者外周血Ig水平的变化,对了解CLL患者免疫功能状态,从而判断病情及预后具有重要作用。     

ZAP-70在24例B细胞慢性淋巴细胞白血病中的表达研究

为了研究慢性淋巴细胞白血病中zeta链相关蛋白-70（zeta-associated protein-70，ZAP-70）的表达及其与其他预后因素的相关性，应用四色流式细胞术检测24例B细胞慢性淋巴细胞白血病（B-CLL）患者骨髓或外周血白血病细胞ZAP-70和CD38的表达。结果显示：①37．5％B-CLL患者表达ZAP-70，其中Binet A期患者有20％（3／15）表达ZAP-70^＋，Binet B＋C期患者有66．7％（6／9）表达ZAP-70^＋，ZAP-70^＋表达在BinetA期和Binet B＋C期之间有显著差异（P〈0．05）；②29．1％B-CLL患者表达CD38，其中Binet A期患者有3例；在此3例中2例同时伴有ZAP-70^＋，CD38^＋在Binet A期和Binet B＋C期之间无显著差异（P〉0．05）；③83．3％（20／24）患者表达ZAP-70^＋CD38^＋或ZAP-70^-CD38^-，ZAP-70和CD38存在相关性（P〈0．05）。结论：在常规实验室可以采用流式细胞术检测ZAP-70，ZAP-70高表达与B-CLL临床分期、染色体及CD38表达等预后相关因素有一定的相关性。