骨髓增生異常綜合征的臨床及生物學研究
發(fā)布時間：2018-09-16 20:04
【摘要】：一、單中心連續(xù)30年2080例MDS的臨床及生物學研究(1984-2013)目的:分析過去連續(xù)30年于本中心初診的2080例MDS患者的臨床及生物學特點,以期揭示我國MDS患者的臨床和生物學特征。方法:1.所有病例按照本實驗室常規(guī)方法進行染色體標本制備及R顯帶分析,進行細胞遺傳學檢查。完善患者基本信息的采集,采用FAB及最新WHO(2008)標準對其進行分型,同時應用IPSS、WPSS及IPSS-R積分系統(tǒng)完善預后分層。2.應用統(tǒng)計學軟件進行統(tǒng)計分析。系統(tǒng)分析2080例MDS患者臨床及細胞遺傳學特點,對550例可隨訪患者完善生存分析。結(jié)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%)�；颊咧形荒挲g51歲(5-93歲),RAS患者中位年齡偏大。男/女比例為1.54:1�？傮w核型異常率為40.3%(839/2080),其中復雜核型為277例,占13.3%(277/2080)。RAEB核型異常率高于其他亞型(RAEBRARASRAEB-tCMML)。生存分析顯示RA預后最好(中位生存期為50月),其次為RAS(中位生存期為32月),最后為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-綜合征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%)。男女比例為1.51:1(898/595)。中位年齡為54歲(6-93歲),外周血Hb中位值為70g/L(11-167 g/L),PLT計數(shù)中位值為51.5×109/L(2~1045×109/L),WBC中位值為2.65×109/L(0.11~52×109/L)。核型異常率為42.1%(628/1493),復雜核型為216例,占14.5%(216/1493)。各亞型間染色體核型異常率差異有統(tǒng)計學意義(P0.01)。預后順序依次為RA/RN/RT/RCUDMDS-URCMDRARSRAEB-1RAEB-2。3.細胞遺傳學:2080例MDS患者中839例含克隆性染色體異常,染色體畸變類型主要以不平衡異常為主,三體或單體最為常見。最常見的克隆性異常是+8,占染色體異�；颊叩�31.2%;其次為-7/del(7q)、del(20q)、del(5q)等。4.生存分析:550例患者分別按照IPSS、IPSS-R、WPSS預后評分系統(tǒng)比較各組生存,均具有顯著差異(P0.001),且COX回歸模型顯示IPSS-R對患者預后判斷要優(yōu)于IPSS及WPSS。結(jié)論:1.我中心MDS患者具有獨特的臨床及生物學特性,與西方國家相比,發(fā)病年齡更為年輕,最常見的染色體核型異常為+8,其次為-7/del(7q)、del(20q)、del(5q)等,與西方國家有顯著差異。2.IPSS-R預后積分系統(tǒng)是判斷MDS患者預后分析更加有力的工具。二、WT1基因在骨髓增生異常綜合征患者中的表達及臨床意義目的:檢測113例初診骨髓增生異常綜合征患者WT1基因的表達,通過回顧性分析,探討WT1基因在MDS各亞型患者中的表達及其與病情進展的關(guān)系和臨床意義。方法:1.通過Q-RT-PCR技術(shù)檢測113例初診MDS患者骨髓標本中WT1基因的表達及abl內(nèi)參基因的表達,WT1基因表達水平=WT1拷貝數(shù)/10000 abl拷貝數(shù)。以WT1基因表達水平300copies/10000 abl copies作為臨界值。2.應用相關(guān)統(tǒng)計學方法分析WT1基因的表達與FAB、WHO分型及IPSS、IPSS-R危險分層的相關(guān)性。并完善113例患者隨訪信息,分析WT1基因?qū)DS患者OS及EFS的預后影響,探討其與病情進展的關(guān)系和臨床意義。結(jié)果:1.WT1基因在MDS各亞型患者中有不同程度表達,表達陽性率為44.2%(50/113)。其表達水平與FAB及WHO分型相關(guān),且隨疾病進展其表達量呈遞增趨勢。FAB分型中RAEB/RAEB-t患者的WT1基因表達水平普遍高于RA/RAS;WHO分型中從RCUD到RCMD、RAEB-1、RAEB-2,WT1基因的表達水平逐漸增高,各亞型間的表達水平存在差異。2.WT1基因的表達與IPSS分層高度相關(guān),隨危險分層的逐級遞增,WT1基因高表達患者所占比例增加,其差異同樣具有統(tǒng)計學意義(P0.05)。3.WT1基因高表達患者預后較低表達組差。單因素分析中兩組OS、EFS均具有顯著差異,P值分別為0.038、0.003;多因素分析顯示,高表達的WT1基因及IPSS-R分層對EFS具有獨立預后意義(P=0.031、P0.001)。4.在原始細胞5%的66例MDS患者中,WT1基因高表達組與低表達組兩者OS有相關(guān)趨勢,但無統(tǒng)計學意義(P=0.088),而EFS差異明顯(P=0.016)。結(jié)論:WT1基因在MDS各亞型患者中有不同程度表達,其表達水平與疾病進展呈正相關(guān),可作為臨床上對MDS病情的高危評估、預測病情變化及判斷預后的重要指標之一。
[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.
【學位授予單位】：蘇州大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：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.
【學位授予單位】：蘇州大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R551.3
【參考文獻】
相關(guān)期刊論文 前3條
1 胡延平;劉璇;陳芳;張男;張e，
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