骨髓增生异常综合征的临床及生物学研究
发布时间：2018-09-16 20:04
【摘要】：一、单中心连续30年2080例MDS的临床及生物学研究(1984-2013)目的:分析过去连续30年于本中心初诊的2080例MDS患者的临床及生物学特点,以期揭示我国MDS患者的临床和生物学特征。方法:1.所有病例按照本实验室常规方法进行染色体标本制备及R显带分析,进行细胞遗传学检查。完善患者基本信息的采集,采用FAB及最新WHO(2008)标准对其进行分型,同时应用IPSS、WPSS及IPSS-R积分系统完善预后分层。2.应用统计学软件进行统计分析。系统分析2080例MDS患者临床及细胞遗传学特点,对550例可随访患者完善生存分析。结果:1.FAB分型:RA 1040例(占50.0%),RARS 135例(占6.5%),RAEB 691例(占33.2%),RAEB-t 145例(占7.0%),CMML 69例(占3.3%)。患者中位年龄51岁(5-93岁),RAS患者中位年龄偏大。男/女比例为1.54:1。总体核型异常率为40.3%(839/2080),其中复杂核型为277例,占13.3%(277/2080)。RAEB核型异常率高于其他亚型(RAEBRARASRAEB-tCMML)。生存分析显示RA预后最好(中位生存期为50月),其次为RAS(中位生存期为32月),最后为RAEB(13月)及RAEB-t(16月)。2.WHO分型:RA/RN/RT/RCUD 220例(占14.7%),RARS 75例(占5.0%),RCMD 385例(占25.8%),5q-综合征14例(占0.9%),RAEB-1患者282例(占18.9%),RAEB-2患者306例(占20.5%),MDS-U 211例(占14.1%)。男女比例为1.51:1(898/595)。中位年龄为54岁(6-93岁),外周血Hb中位值为70g/L(11-167 g/L),PLT计数中位值为51.5×109/L(2~1045×109/L),WBC中位值为2.65×109/L(0.11~52×109/L)。核型异常率为42.1%(628/1493),复杂核型为216例,占14.5%(216/1493)。各亚型间染色体核型异常率差异有统计学意义(P0.01)。预后顺序依次为RA/RN/RT/RCUDMDS-URCMDRARSRAEB-1RAEB-2。3.细胞遗传学:2080例MDS患者中839例含克隆性染色体异常,染色体畸变类型主要以不平衡异常为主,三体或单体最为常见。最常见的克隆性异常是+8,占染色体异常患者的31.2%;其次为-7/del(7q)、del(20q)、del(5q)等。4.生存分析:550例患者分别按照IPSS、IPSS-R、WPSS预后评分系统比较各组生存,均具有显著差异(P0.001),且COX回归模型显示IPSS-R对患者预后判断要优于IPSS及WPSS。结论:1.我中心MDS患者具有独特的临床及生物学特性,与西方国家相比,发病年龄更为年轻,最常见的染色体核型异常为+8,其次为-7/del(7q)、del(20q)、del(5q)等,与西方国家有显著差异。2.IPSS-R预后积分系统是判断MDS患者预后分析更加有力的工具。二、WT1基因在骨髓增生异常综合征患者中的表达及临床意义目的:检测113例初诊骨髓增生异常综合征患者WT1基因的表达,通过回顾性分析,探讨WT1基因在MDS各亚型患者中的表达及其与病情进展的关系和临床意义。方法:1.通过Q-RT-PCR技术检测113例初诊MDS患者骨髓标本中WT1基因的表达及abl内参基因的表达,WT1基因表达水平=WT1拷贝数/10000 abl拷贝数。以WT1基因表达水平300copies/10000 abl copies作为临界值。2.应用相关统计学方法分析WT1基因的表达与FAB、WHO分型及IPSS、IPSS-R危险分层的相关性。并完善113例患者随访信息,分析WT1基因对MDS患者OS及EFS的预后影响,探讨其与病情进展的关系和临床意义。结果:1.WT1基因在MDS各亚型患者中有不同程度表达,表达阳性率为44.2%(50/113)。其表达水平与FAB及WHO分型相关,且随疾病进展其表达量呈递增趋势。FAB分型中RAEB/RAEB-t患者的WT1基因表达水平普遍高于RA/RAS;WHO分型中从RCUD到RCMD、RAEB-1、RAEB-2,WT1基因的表达水平逐渐增高,各亚型间的表达水平存在差异。2.WT1基因的表达与IPSS分层高度相关,随危险分层的逐级递增,WT1基因高表达患者所占比例增加,其差异同样具有统计学意义(P0.05)。3.WT1基因高表达患者预后较低表达组差。单因素分析中两组OS、EFS均具有显著差异,P值分别为0.038、0.003;多因素分析显示,高表达的WT1基因及IPSS-R分层对EFS具有独立预后意义(P=0.031、P0.001)。4.在原始细胞5%的66例MDS患者中,WT1基因高表达组与低表达组两者OS有相关趋势,但无统计学意义(P=0.088),而EFS差异明显(P=0.016)。结论:WT1基因在MDS各亚型患者中有不同程度表达,其表达水平与疾病进展呈正相关,可作为临床上对MDS病情的高危评估、预测病情变化及判断预后的重要指标之一。
[Abstract]:Objective: To analyze the clinical and biological characteristics of 2 080 cases of MDS newly diagnosed in our center in the past 30 years in order to reveal the clinical and biological characteristics of MDS patients in China. Prepare and R-banding analysis, carry out cytogenetic examination, improve the collection of patients'basic information, use FAB and the latest WHO (2008) standard to classify them, and use IPSS, WPSS and IPSS-R integral system to improve the prognosis stratification. 2. Statistical analysis software was used to analyze the clinical and cytogenetic characteristics of 2080 MDS patients. Results: 1. FAB classification: RA 1040 cases (50.0%), RARS 135 cases (6.5%), RAEB 691 cases (33.2%), RAEB-t 145 cases (7.0%), CMML 69 cases (3.3%). The abnormal rate of RAEB karyotype was higher than that of other subtypes (RAEBRARASRAEB-tCMML). Survival analysis showed that the prognosis of RA was the best (median survival time was October), followed by RAS (median survival time was 32 months), RAEB (13 months) and RAEB-t (16 months). 2. WHO classification: RA/RN/RT/RCUD 220 (14.7%), RARS 75 (5.0%) and RCMD 3. 85 cases (25.8%), 14 cases (0.9%) of 5q-syndrome, 282 cases (18.9%) of RAEB-1, 306 cases (20.5%) of RAEB-2, 211 cases (14.1%) of MDS-U. The male-female ratio was 1.51:1 (898/595). The median age was 54 years (6-93 years), the median value of Hb in peripheral blood was 70 g/L (11-167 g/L), the median value of PLT was 51.5 *109/L (2-1045 *109/L), and the median value of WBC was 2.65 *109/L. L(0.11~52 *109/L). The abnormal rate of karyotype was 42.1%(628/1493) and complex karyotype was 216 (14.5%(216/1493). The abnormal rate of chromosome karyotype was significantly different among the subtypes (P 0.01). The sequence of prognosis was RA/RN/RT/RCUDMDS-URCMDRARSRAEB-1 RAEB-2.3. Cytogenetics: 839 of 2080 patients with MDS contained clonal chromosomal abnormalities and staining. The most common clonal abnormality was +8, accounting for 31.2% of the patients with chromosomal abnormalities, followed by - 7/del (7q), del (20q), del (5q) and so on. 4. Survival analysis: 550 patients were compared according to IPSS, IPSS-R, WPSS prognostic scoring system survival, there were significant differences (P 0.00). COX regression model showed that IPSS-R was superior to IPSS and WPSS in predicting the prognosis of patients. Conclusion: 1. MDS patients in our center had unique clinical and biological characteristics. Compared with Western countries, the age of onset was younger. The most common chromosomal abnormalities were +8, followed by - 7/del (7q), del (20q), del (5q), and so on, which were significantly different from those in Western countries. 2. IPSS-R prognostic score system is a more powerful tool for judging the prognosis of MDS patients. 2. Expression of WT1 gene in myelodysplastic syndrome patients and its clinical significance Objective: To detect the expression of WT1 gene in 113 newly diagnosed patients with myelodysplastic syndrome, and to explore the expression of WT1 gene in MDS subtypes by retrospective analysis. Methods: 1. The expression of WT1 gene and ABL internal reference gene were detected by Q-RT-PCR in 113 newly diagnosed MDS patients'bone marrow samples. The expression level of WT1 gene was equal to WT1 copy number/10000 ABL copy number. The correlation between WT1 gene expression and FAB, WHO classification, IPSS and IPSS-R risk stratification was analyzed statistically. The follow-up information of 113 patients was improved, and the prognostic effect of WT1 gene on OS and EFS in MDS patients was analyzed. The relationship between WT1 gene expression and disease progression and its clinical significance were discussed. The positive rate was 44.2%(50/113). The expression level of WT1 gene was correlated with FAB and WHO classification, and increased with the progression of the disease. The expression of WT1 gene was highly correlated with IPSS stratification. With the increase of risk stratification, the proportion of patients with high WT1 gene expression increased. The difference was also statistically significant (P 0.05). 3. The prognosis of patients with high WT1 gene expression was poor in the low expression group. Multivariate analysis showed that high expression of WT1 gene and IPSS-R stratification had independent prognostic significance for EFS (P = 0.031, P 0.001). 4. In 66 MDS patients with 5% primordial cells, OS of WT1 gene high expression group and low expression group had a correlation trend, but no statistical significance (P = 0.088), while EFS had significant difference (P = 0.016). The expression level of MDS is positively correlated with the progression of the disease. It can be used as one of the important indexes to evaluate the risk of MDS, predict the changes of the disease and judge the prognosis.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R551.3
[Abstract]:Objective: To analyze the clinical and biological characteristics of 2 080 cases of MDS newly diagnosed in our center in the past 30 years in order to reveal the clinical and biological characteristics of MDS patients in China. Prepare and R-banding analysis, carry out cytogenetic examination, improve the collection of patients'basic information, use FAB and the latest WHO (2008) standard to classify them, and use IPSS, WPSS and IPSS-R integral system to improve the prognosis stratification. 2. Statistical analysis software was used to analyze the clinical and cytogenetic characteristics of 2080 MDS patients. Results: 1. FAB classification: RA 1040 cases (50.0%), RARS 135 cases (6.5%), RAEB 691 cases (33.2%), RAEB-t 145 cases (7.0%), CMML 69 cases (3.3%). The abnormal rate of RAEB karyotype was higher than that of other subtypes (RAEBRARASRAEB-tCMML). Survival analysis showed that the prognosis of RA was the best (median survival time was October), followed by RAS (median survival time was 32 months), RAEB (13 months) and RAEB-t (16 months). 2. WHO classification: RA/RN/RT/RCUD 220 (14.7%), RARS 75 (5.0%) and RCMD 3. 85 cases (25.8%), 14 cases (0.9%) of 5q-syndrome, 282 cases (18.9%) of RAEB-1, 306 cases (20.5%) of RAEB-2, 211 cases (14.1%) of MDS-U. The male-female ratio was 1.51:1 (898/595). The median age was 54 years (6-93 years), the median value of Hb in peripheral blood was 70 g/L (11-167 g/L), the median value of PLT was 51.5 *109/L (2-1045 *109/L), and the median value of WBC was 2.65 *109/L. L(0.11~52 *109/L). The abnormal rate of karyotype was 42.1%(628/1493) and complex karyotype was 216 (14.5%(216/1493). The abnormal rate of chromosome karyotype was significantly different among the subtypes (P 0.01). The sequence of prognosis was RA/RN/RT/RCUDMDS-URCMDRARSRAEB-1 RAEB-2.3. Cytogenetics: 839 of 2080 patients with MDS contained clonal chromosomal abnormalities and staining. The most common clonal abnormality was +8, accounting for 31.2% of the patients with chromosomal abnormalities, followed by - 7/del (7q), del (20q), del (5q) and so on. 4. Survival analysis: 550 patients were compared according to IPSS, IPSS-R, WPSS prognostic scoring system survival, there were significant differences (P 0.00). COX regression model showed that IPSS-R was superior to IPSS and WPSS in predicting the prognosis of patients. Conclusion: 1. MDS patients in our center had unique clinical and biological characteristics. Compared with Western countries, the age of onset was younger. The most common chromosomal abnormalities were +8, followed by - 7/del (7q), del (20q), del (5q), and so on, which were significantly different from those in Western countries. 2. IPSS-R prognostic score system is a more powerful tool for judging the prognosis of MDS patients. 2. Expression of WT1 gene in myelodysplastic syndrome patients and its clinical significance Objective: To detect the expression of WT1 gene in 113 newly diagnosed patients with myelodysplastic syndrome, and to explore the expression of WT1 gene in MDS subtypes by retrospective analysis. Methods: 1. The expression of WT1 gene and ABL internal reference gene were detected by Q-RT-PCR in 113 newly diagnosed MDS patients'bone marrow samples. The expression level of WT1 gene was equal to WT1 copy number/10000 ABL copy number. The correlation between WT1 gene expression and FAB, WHO classification, IPSS and IPSS-R risk stratification was analyzed statistically. The follow-up information of 113 patients was improved, and the prognostic effect of WT1 gene on OS and EFS in MDS patients was analyzed. The relationship between WT1 gene expression and disease progression and its clinical significance were discussed. The positive rate was 44.2%(50/113). The expression level of WT1 gene was correlated with FAB and WHO classification, and increased with the progression of the disease. The expression of WT1 gene was highly correlated with IPSS stratification. With the increase of risk stratification, the proportion of patients with high WT1 gene expression increased. The difference was also statistically significant (P 0.05). 3. The prognosis of patients with high WT1 gene expression was poor in the low expression group. Multivariate analysis showed that high expression of WT1 gene and IPSS-R stratification had independent prognostic significance for EFS (P = 0.031, P 0.001). 4. In 66 MDS patients with 5% primordial cells, OS of WT1 gene high expression group and low expression group had a correlation trend, but no statistical significance (P = 0.088), while EFS had significant difference (P = 0.016). The expression level of MDS is positively correlated with the progression of the disease. It can be used as one of the important indexes to evaluate the risk of MDS, predict the changes of the disease and judge the prognosis.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R551.3
【参考文献】
相关期刊论文 前3条
1 胡延平;刘璇;陈芳;张男;张e，
本文编号：2244641
本文链接：https://www.wllwen.com/yixuelunwen/xxg/2244641.html
最近更新
教材专著
