原发性骨髓增生异常综合征患者细胞遗传学异常特征及其临床意义
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摘要
研究目的
研究原发性骨髓增生异常综合征(MDS)患者染色体核型特征。
研究方法
对染色体核型可供分析的351例成人原发MDS患者进行回顾性分析。
结果
染色体核型异常者237例(67.5%)。其中仅有染色体数目异常者99例(41.7%),仅有染色体结构异常者70例(29.5%),同时有数目与结构异常者68例(28.8%);单一异常130例(54.8%),2种异常54例(22.8%),复杂异常(≥3种)53例(22.4%)。整倍体数目改变有多倍体4例(1.7%);非整倍体及染色体臂的异常可见于所有染色体,常见的依次有+8、-20/20q-、-7/7q-、-5/5q-、-18、-11/11q-、+21、-Y、-21、-10、-16、-22、+9、del(12)(p12)。-5/5q-(5.1%)的发生率低于西方国家(8.7%-23.4%),5q-综合征的发生率极低(0.3%),+8(19.1%)和-20/20q-(9.4%)发生率高于西方国家(分别为1.2%-7.0%和2.0%-3.5%)。237例染色体核型异常的患者中染色体易位有31例(13.1%),其中12种染色体易位在MDS中迄今尚无文献报道。i(17)(q10)有9例(3.8%),其中6例(66.7%)为单一异常。染色体重复有7例(3.0%),主要累及1号染色体(4例)。按IPSS染色体核型分组,预后差的染色体核型检出率在RA、RARS、5q-综合征组,RCMD、RCMDRS组,RAEB-Ⅰ组,RAEB-Ⅱ组依次升高,差异有统计学意义(χ~2=2.854,p＜0.001)。
结论
我国MDS患者具有有别于西方国家MDS患者的染色体核型异常特征。
研究目的
探索RAD51_(G135C)、XRCC3_(C241T)多态性位点和GSTT1、GSTM1基因型与原发性骨髓增生异常综合征(MDS)易感性及其染色体核型异常之间的关系。
研究方法
对381例原发性成人MDS患者和443名与患者无血缘关系的正常人群对照,用PCR-RFLP方法分析RAD51_(G135C)、XRCC3_(C241T)多态性位点基因型,用多重PCR方法检测GSTT1和GSTM1基因型。
结果
MDS患者RAD51_(G135C)纯合基因型频率高于正常对照组(6.9%vs.3.6%,p=0.037),纯合型是发生MDS的危险因素(p=0.037,OR=2.01,95%CI 1.03～3.91),该结果在多因素分析排除年龄和性别因素对基因型分布的影响后更加显著(p=0.029,OR=2.12,95%CI 1.08～4.17),在各基因型联合效应分析中也能独立相关(p=0.005,OR=2.61,95%CI 1.34～5.11)。
RAD51_(G135C)纯合型在染色体正常患者中的比例较对照组明显升高(9.9%vs.3.6%),发生染色体正常MDS的风险增高(p=0.005,OR=2.92,95%CI 1.33～6.41)。
在复杂核型异常(≥3种异常)的患者中GSTT1 null型比例明显升高(78.3%),GSTT1 null型患复杂核型异常MDS的风险是present型的4.79倍,该风险在多因素分析排除年龄和性别因素对基因型分布的影响后仍有统计学意义(p=0.009,OR=3.96,95%CI 1.42～11.10)。另外,有GSTM1分析结果的5例-5/5q-患者均为null型。
多因素分析以年龄、性别、是否从事风险职业(风险职业包括接触苯类物质、汽油、柴油、油漆、甲醛、杀虫剂、除草剂、化肥、放射性物质的职业)、有无非职业暴露因素(非职业暴露因素包括吸烟、饮酒、染发、居住环境新装修且有异味)、WHO分组(RA+RARS+5q-综合征/RCMD+RCMDRS/RAEB-Ⅰ/RAEB-Ⅱ)及基因型作为协变量,基因型与MDS中染色体异常的相关关系无统计学意义。
结论
1.本研究发现RAD51_(G135C)纯合基因型是我国成人原发性MDS发生的危险因素,但未发现XRCC3_(C241T)、GSTT1、GSTM1基因null型与我国成人原发性MDS发生有关。
2.RAD51_(G135C)纯合基因型与染色体正常的MDS发生有关;GSTT1基因null型与MDS中染色体复杂核型异常有关。
3.遗传因素与环境因素共同作用于造血干/祖细胞导致其克隆性改变是MDS发生的关键。
研究目的
研究原发性骨髓增生异常综合征(MDS)患者染色体核型异常的预后意义。
研究方法
对染色体核型可供分析的且随访资料完整的164例成人原发性MDS患者进行回顾性分析。
结果
164例患者中有82例死亡,中位随访时间19(1～138)个月,中位生存(MS)期36个月,2年预期生存(PS)率60%,5年PS率42%。染色体异常患者为113例(68.9%)。其中单一异常有45例,MDS中重现性单一异常核型+8、20q-、-5/5q-、-Y、i(17)(q10)分别为13、7、4、1、6例。染色体异常的患者中,累及7号染色体异常者为24例。按WPSS染色体核型分组,染色体核型为预后好、中、差的患者MS分别为57[95%可信区间(CI)(95%CI 37～77)]个月、37(95%CI 20～54)个月和12(95%CI 6～17)个月,Log rank检验三组总体生存(OS)率差异有统计学意义(p＜0.001)。按正常核型(NN)-嵌合核型(AN)-异常核型(AA)分组,NN、AN、AA患者MS分别为59(95%CI 48～71)个月、37(95%CI 14～60)个月和23(95%CI 11～34)个月,Log rank检验三组OS率差异有统计学意义(p=0.022)。单一异常核型的患者中,+8、20q-、-5/5q-、-Y、i(17q)分别与其他单一异常核型患者比较生存期均无统计学差异(p＞0.05)。累及7号染色体异常的24例患者MS为10(95%CI 4～16)个月,较其他核型异常的患者MS分别为51(95%CI 30～72)个月明显缩短(p＜0.001)。按WPSS评分,极低危组、低危组、中危组、高危组和极高危组的2年PS率分别为100%、96%、81%、38%和14%,5年PS率分别为100%、83%、54%、20%和0,Log rank检验各组总体生存(OS)率差异有统计学意义(P＜0.001)。
结论
染色体核型分析是MDS患者预后分层实现个体化治疗的重要依据。与WHO分型相适应的WPSS适合用于判断我国MDS患者的预后。
Objective
To investigate the cytogenetic features of primary myelodysplastic syndromes(MDS) in Chinese adult patients.
Methods
Three hundred and fifty-one adult patients with primary MDS were retrospectively analyzed for their chromosomal abnormalities by karyotyping.
Results
Two hundred and thirty-seven cases(67.5%) demonstrated karyotypic abnormalities, including 99 with copy number changes alone(41.7%),70 with structural abnormalities alone(29.5%),and 68 with both of these changes(28.8%).In addition,among the 237 patients with chromosomal abnormalities,130 cases(54.8%) showed single abnormality,54 cases(22.8%) showed double abnormalities and 53 cases(22.4%) showed complex abnormalities(more than two independent aberrations).Four cases(1.7%) were multiploid. Aneuploidy or anomaly of chromosomal arm were detected across all of the 24 chromosomes and the aberrations frequently seen were +8,-20/20q-,-7/7q-,-5/5q-,-18, -11/11q-/,+21,-Y,-21,-10,-16,-22,+9,del(12)(p12) in order.Overall,the frequency of -5/5q-/del(5)(q13-33) was 5.1%in these Chinese MDS patients,which was lower than that in the MDS patients of western countries(8.7-23.4%),and the incidence of 5q-syndrome was only 0.3%in Chinese MDS patients.On the other hand,the frequencies of trisomy 8 (19.1%) and -20/20q-/del(20)(q11-13)(9.4%) were higher than those in western countries (1.2-7.0%and 2.0-3.5%,respectively).Chromosomal translocations were also detected in 31 cases(13.1%) including 12 rare translocations that have not been reported in MDS patients before.In addition,i(17)(q10)was detected in nine cases(3.8%),of which six cases only had this single abnormality.According to the IPSS chromosomal prognostic classification,the incidence of poor-risk karyotypes increased in the advanced WHO subtypes(p＜0.001).
Conclusion
Together,we detected the unique cytogenetic features of chromosomal abnormalities.
Objective
To investigate the impact of RAD51_(G135C),XRCC3_(C241T),GSTM1 and GSTT1 genotypes on the myelodysplastic syndromes(MDS) susceptibility and chromosomal abnormalities of MDS.
Methods
RAD51_(G135C),XRCC3_(C241T),GSTT1 and GSTM1 genotypes were detected in 381 adult patients with de novo MDS and 443 healthy controls with comparable age and gender by PCR-RFLP or multi-PCR.
Results
There was a significant difference of the incidence of RAD51G135C C/C genotype between MDS patients and controls(6.9%vs.3.6%,p=0.037).The odds ratio of this genotype for MDS risk was 2.01(p=0.037,95%CI 1.03～3.91),which was more significant in the multi-factor analysis including age and gender.RAD51G135C C/C genotype remained independently associated with risk of MDS when the joint effect of other genes were considered(p=0.005,OR=2.61,95%CI 1.34～5.11).
Moreover,in individuals with normal chromosomal karyotypes,the incidence of RAD51G135C C/C genotype was higher than that in healthy controls(9.9%vs.3.6%). The odds ratio for risk of the normal karyotypic group was 2.92.
In individuals with complex chromosomal abnormalities(at least 3 abnormal karyotypes), the incidence of GSTT1 null genotype was higher than in controls.The odds ratio for risk of the complex karyotypic MDS was elevated to 4.79,which was still significant as consideration of age and gender(p=0.009,OR=3.96,95%CI 1.42～11.10).Interestingly, the 5 case of -5/5q- were all with GSTM1 null genotypes.
Furthermore,the multi-factor analysis including age,gender,occupational risk factor,non-occupationl risk,WHO subgroups and genotypes showed no significant association between any genotype and chromosomal abnormality in MDS.
Conclusion
RAD51_(G135C) C/C genotype is the genetic susceptible factor for Chinese adult patients with primary MDS.XRCC3_(C241T) genotype and null genotype of GSTT1 or GSTM1 were not independently associated with the occurrence of MDS.RAD51_(G135C) C/C genotype was relative to MDS with normal karyotype while GSTT1 was relative to MDS with complex abnormal karyotype.Genes in the pathway of DNA DSBs repair and toxin metaboly affected the pathogenesis of MDS in which both genetic factors and environmental factors were involved.
Objective
To investigate the prognostic significance of chromosomal karyotype in patients with primary myelodysplastic syndromes(MDS).
Methods
One hundred and sixty-four adult patients with valid results of chromosomal karyotype and successfully followed up were retrospectively analyzed.
Results
Among the 164 patients,82 died.The median follow-up time was 19(1-138) months and the median survival was 36 months.2-year survival was 60%and 5-year survival was 42%.One hundred and thirteen cases(68.9%) demonstrated karyotypic abnormalities.Of those,45 showed single abnormality.As isolated abnormalities,there were 13 cases with +8,7 cases with -20/20q-,4 cases with -5/5q-,one case with -Y and 6 cases with i(17)(q10),which were recurrently seen in MDS.When it came to aberrance involved chromosomal 7,24 cases were detected either single or together with other abnormalities. According to WPSS chromosomal prognositic classification,the median OS of patients with good,intermediate and poor-risk cytogenetic subgroup were 57(95%CI 37-77), 37(95%CI 20-54),12(95%CI 6-17) months,respectively(p＜0.001).According to NN-AN-AA classification of karyotype,the median OS of patients with NN,AN,AA were 59(95%CI 48-71),37(95%CI 14-60),23(95%CI 11-34) months,respectively(p =0.022).In patients with very low-risk,low-risk,intermediate-risk,high-risk and very high-risk stratified by WPSS,2-year survival were 100%,96%,81%,38%and 14%, respectively;5-year survival were 100%,83%,54%,20%and 0,respectively(p＜0.001).
Conclusion
Chromosomal karyotype is of great importance in revealing prognosis to achieve individual therapy in MDS.In addition,WPSS based on WHO classification was adapted to prognostic determination in Chinese patients with MDS.
研究原发性骨髓增生异常综合征(MDS)患者染色体核型特征。
研究方法
对染色体核型可供分析的351例成人原发MDS患者进行回顾性分析。
结果
染色体核型异常者237例(67.5%)。其中仅有染色体数目异常者99例(41.7%),仅有染色体结构异常者70例(29.5%),同时有数目与结构异常者68例(28.8%);单一异常130例(54.8%),2种异常54例(22.8%),复杂异常(≥3种)53例(22.4%)。整倍体数目改变有多倍体4例(1.7%);非整倍体及染色体臂的异常可见于所有染色体,常见的依次有+8、-20/20q-、-7/7q-、-5/5q-、-18、-11/11q-、+21、-Y、-21、-10、-16、-22、+9、del(12)(p12)。-5/5q-(5.1%)的发生率低于西方国家(8.7%-23.4%),5q-综合征的发生率极低(0.3%),+8(19.1%)和-20/20q-(9.4%)发生率高于西方国家(分别为1.2%-7.0%和2.0%-3.5%)。237例染色体核型异常的患者中染色体易位有31例(13.1%),其中12种染色体易位在MDS中迄今尚无文献报道。i(17)(q10)有9例(3.8%),其中6例(66.7%)为单一异常。染色体重复有7例(3.0%),主要累及1号染色体(4例)。按IPSS染色体核型分组,预后差的染色体核型检出率在RA、RARS、5q-综合征组,RCMD、RCMDRS组,RAEB-Ⅰ组,RAEB-Ⅱ组依次升高,差异有统计学意义(χ~2=2.854,p＜0.001)。
结论
我国MDS患者具有有别于西方国家MDS患者的染色体核型异常特征。
研究目的
探索RAD51_(G135C)、XRCC3_(C241T)多态性位点和GSTT1、GSTM1基因型与原发性骨髓增生异常综合征(MDS)易感性及其染色体核型异常之间的关系。
研究方法
对381例原发性成人MDS患者和443名与患者无血缘关系的正常人群对照,用PCR-RFLP方法分析RAD51_(G135C)、XRCC3_(C241T)多态性位点基因型,用多重PCR方法检测GSTT1和GSTM1基因型。
结果
MDS患者RAD51_(G135C)纯合基因型频率高于正常对照组(6.9%vs.3.6%,p=0.037),纯合型是发生MDS的危险因素(p=0.037,OR=2.01,95%CI 1.03～3.91),该结果在多因素分析排除年龄和性别因素对基因型分布的影响后更加显著(p=0.029,OR=2.12,95%CI 1.08～4.17),在各基因型联合效应分析中也能独立相关(p=0.005,OR=2.61,95%CI 1.34～5.11)。
RAD51_(G135C)纯合型在染色体正常患者中的比例较对照组明显升高(9.9%vs.3.6%),发生染色体正常MDS的风险增高(p=0.005,OR=2.92,95%CI 1.33～6.41)。
在复杂核型异常(≥3种异常)的患者中GSTT1 null型比例明显升高(78.3%),GSTT1 null型患复杂核型异常MDS的风险是present型的4.79倍,该风险在多因素分析排除年龄和性别因素对基因型分布的影响后仍有统计学意义(p=0.009,OR=3.96,95%CI 1.42～11.10)。另外,有GSTM1分析结果的5例-5/5q-患者均为null型。
多因素分析以年龄、性别、是否从事风险职业(风险职业包括接触苯类物质、汽油、柴油、油漆、甲醛、杀虫剂、除草剂、化肥、放射性物质的职业)、有无非职业暴露因素(非职业暴露因素包括吸烟、饮酒、染发、居住环境新装修且有异味)、WHO分组(RA+RARS+5q-综合征/RCMD+RCMDRS/RAEB-Ⅰ/RAEB-Ⅱ)及基因型作为协变量,基因型与MDS中染色体异常的相关关系无统计学意义。
结论
1.本研究发现RAD51_(G135C)纯合基因型是我国成人原发性MDS发生的危险因素,但未发现XRCC3_(C241T)、GSTT1、GSTM1基因null型与我国成人原发性MDS发生有关。
2.RAD51_(G135C)纯合基因型与染色体正常的MDS发生有关;GSTT1基因null型与MDS中染色体复杂核型异常有关。
3.遗传因素与环境因素共同作用于造血干/祖细胞导致其克隆性改变是MDS发生的关键。
研究目的
研究原发性骨髓增生异常综合征(MDS)患者染色体核型异常的预后意义。
研究方法
对染色体核型可供分析的且随访资料完整的164例成人原发性MDS患者进行回顾性分析。
结果
164例患者中有82例死亡,中位随访时间19(1～138)个月,中位生存(MS)期36个月,2年预期生存(PS)率60%,5年PS率42%。染色体异常患者为113例(68.9%)。其中单一异常有45例,MDS中重现性单一异常核型+8、20q-、-5/5q-、-Y、i(17)(q10)分别为13、7、4、1、6例。染色体异常的患者中,累及7号染色体异常者为24例。按WPSS染色体核型分组,染色体核型为预后好、中、差的患者MS分别为57[95%可信区间(CI)(95%CI 37～77)]个月、37(95%CI 20～54)个月和12(95%CI 6～17)个月,Log rank检验三组总体生存(OS)率差异有统计学意义(p＜0.001)。按正常核型(NN)-嵌合核型(AN)-异常核型(AA)分组,NN、AN、AA患者MS分别为59(95%CI 48～71)个月、37(95%CI 14～60)个月和23(95%CI 11～34)个月,Log rank检验三组OS率差异有统计学意义(p=0.022)。单一异常核型的患者中,+8、20q-、-5/5q-、-Y、i(17q)分别与其他单一异常核型患者比较生存期均无统计学差异(p＞0.05)。累及7号染色体异常的24例患者MS为10(95%CI 4～16)个月,较其他核型异常的患者MS分别为51(95%CI 30～72)个月明显缩短(p＜0.001)。按WPSS评分,极低危组、低危组、中危组、高危组和极高危组的2年PS率分别为100%、96%、81%、38%和14%,5年PS率分别为100%、83%、54%、20%和0,Log rank检验各组总体生存(OS)率差异有统计学意义(P＜0.001)。
结论
染色体核型分析是MDS患者预后分层实现个体化治疗的重要依据。与WHO分型相适应的WPSS适合用于判断我国MDS患者的预后。
Objective
To investigate the cytogenetic features of primary myelodysplastic syndromes(MDS) in Chinese adult patients.
Methods
Three hundred and fifty-one adult patients with primary MDS were retrospectively analyzed for their chromosomal abnormalities by karyotyping.
Results
Two hundred and thirty-seven cases(67.5%) demonstrated karyotypic abnormalities, including 99 with copy number changes alone(41.7%),70 with structural abnormalities alone(29.5%),and 68 with both of these changes(28.8%).In addition,among the 237 patients with chromosomal abnormalities,130 cases(54.8%) showed single abnormality,54 cases(22.8%) showed double abnormalities and 53 cases(22.4%) showed complex abnormalities(more than two independent aberrations).Four cases(1.7%) were multiploid. Aneuploidy or anomaly of chromosomal arm were detected across all of the 24 chromosomes and the aberrations frequently seen were +8,-20/20q-,-7/7q-,-5/5q-,-18, -11/11q-/,+21,-Y,-21,-10,-16,-22,+9,del(12)(p12) in order.Overall,the frequency of -5/5q-/del(5)(q13-33) was 5.1%in these Chinese MDS patients,which was lower than that in the MDS patients of western countries(8.7-23.4%),and the incidence of 5q-syndrome was only 0.3%in Chinese MDS patients.On the other hand,the frequencies of trisomy 8 (19.1%) and -20/20q-/del(20)(q11-13)(9.4%) were higher than those in western countries (1.2-7.0%and 2.0-3.5%,respectively).Chromosomal translocations were also detected in 31 cases(13.1%) including 12 rare translocations that have not been reported in MDS patients before.In addition,i(17)(q10)was detected in nine cases(3.8%),of which six cases only had this single abnormality.According to the IPSS chromosomal prognostic classification,the incidence of poor-risk karyotypes increased in the advanced WHO subtypes(p＜0.001).
Conclusion
Together,we detected the unique cytogenetic features of chromosomal abnormalities.
Objective
To investigate the impact of RAD51_(G135C),XRCC3_(C241T),GSTM1 and GSTT1 genotypes on the myelodysplastic syndromes(MDS) susceptibility and chromosomal abnormalities of MDS.
Methods
RAD51_(G135C),XRCC3_(C241T),GSTT1 and GSTM1 genotypes were detected in 381 adult patients with de novo MDS and 443 healthy controls with comparable age and gender by PCR-RFLP or multi-PCR.
Results
There was a significant difference of the incidence of RAD51G135C C/C genotype between MDS patients and controls(6.9%vs.3.6%,p=0.037).The odds ratio of this genotype for MDS risk was 2.01(p=0.037,95%CI 1.03～3.91),which was more significant in the multi-factor analysis including age and gender.RAD51G135C C/C genotype remained independently associated with risk of MDS when the joint effect of other genes were considered(p=0.005,OR=2.61,95%CI 1.34～5.11).
Moreover,in individuals with normal chromosomal karyotypes,the incidence of RAD51G135C C/C genotype was higher than that in healthy controls(9.9%vs.3.6%). The odds ratio for risk of the normal karyotypic group was 2.92.
In individuals with complex chromosomal abnormalities(at least 3 abnormal karyotypes), the incidence of GSTT1 null genotype was higher than in controls.The odds ratio for risk of the complex karyotypic MDS was elevated to 4.79,which was still significant as consideration of age and gender(p=0.009,OR=3.96,95%CI 1.42～11.10).Interestingly, the 5 case of -5/5q- were all with GSTM1 null genotypes.
Furthermore,the multi-factor analysis including age,gender,occupational risk factor,non-occupationl risk,WHO subgroups and genotypes showed no significant association between any genotype and chromosomal abnormality in MDS.
Conclusion
RAD51_(G135C) C/C genotype is the genetic susceptible factor for Chinese adult patients with primary MDS.XRCC3_(C241T) genotype and null genotype of GSTT1 or GSTM1 were not independently associated with the occurrence of MDS.RAD51_(G135C) C/C genotype was relative to MDS with normal karyotype while GSTT1 was relative to MDS with complex abnormal karyotype.Genes in the pathway of DNA DSBs repair and toxin metaboly affected the pathogenesis of MDS in which both genetic factors and environmental factors were involved.
Objective
To investigate the prognostic significance of chromosomal karyotype in patients with primary myelodysplastic syndromes(MDS).
Methods
One hundred and sixty-four adult patients with valid results of chromosomal karyotype and successfully followed up were retrospectively analyzed.
Results
Among the 164 patients,82 died.The median follow-up time was 19(1-138) months and the median survival was 36 months.2-year survival was 60%and 5-year survival was 42%.One hundred and thirteen cases(68.9%) demonstrated karyotypic abnormalities.Of those,45 showed single abnormality.As isolated abnormalities,there were 13 cases with +8,7 cases with -20/20q-,4 cases with -5/5q-,one case with -Y and 6 cases with i(17)(q10),which were recurrently seen in MDS.When it came to aberrance involved chromosomal 7,24 cases were detected either single or together with other abnormalities. According to WPSS chromosomal prognositic classification,the median OS of patients with good,intermediate and poor-risk cytogenetic subgroup were 57(95%CI 37-77), 37(95%CI 20-54),12(95%CI 6-17) months,respectively(p＜0.001).According to NN-AN-AA classification of karyotype,the median OS of patients with NN,AN,AA were 59(95%CI 48-71),37(95%CI 14-60),23(95%CI 11-34) months,respectively(p =0.022).In patients with very low-risk,low-risk,intermediate-risk,high-risk and very high-risk stratified by WPSS,2-year survival were 100%,96%,81%,38%and 14%, respectively;5-year survival were 100%,83%,54%,20%and 0,respectively(p＜0.001).
Conclusion
Chromosomal karyotype is of great importance in revealing prognosis to achieve individual therapy in MDS.In addition,WPSS based on WHO classification was adapted to prognostic determination in Chinese patients with MDS.
引文
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[3]Chen B,Zhao WL,Jin J et al.Clinical and cytogenetic features of 508 Chinese patients with myelodysplastic syndrome and comparison with those in Western countries.Leukemia,2005,19:767-775.
[4]Matsuda A,Germing U,Jinnai I,et al.Difference in clinical features between Japanese and German patients with refractory anemia in myelodysplastic syndromes.Blood,2005,106:2633-2640.
[5]Lee JH,Lee JH,Shin YR,et al.Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome Leukemia,2003,17:305-313.
[6]Intragumtornchai T,Prayoonwiwat W,Swasdikul D,et al.Myelodysplastic syndromes in Thailand:a retrospective pathologic and clinical analysis of 117 cases.Leuk Res,1998,22:453-460.
[7]Vardiman JW,Harris NL,Brunning RD,et al.The World Health Organization (WHO)classification of the myeloid neoplasms.Blood,2002,100:2292-2302.
[8]Greenberg P,Cox C,LeBeau M,et al.International Scoring System for Evaluating Prognosis in myelodysplastic syndromes.Blood,1997,89:2079-2088.
[9]Tiu R,Gondek L,O'Keefe C,et al.Clonality of the stem cell compartment during evolution of myelodysplastic syndromes and other bone marrow failure syndromes.Leukemia,2007,21:1648-1657
[10]Virtaneva K,Writht FA,Tanner SM,et al.Expression profiling reveal fundamental biological differences in acute myeloid leukemia with isolated trosomy 8 and normal cytogenetics.Proc Natl Acad Sci U S A,2001,98:1124-1129.
[11]Xiao Z,Liu Z,Yu M,et al.Ischromosome 17q in patients with myelodysplastic syndromes:six new cases.Haematologica,2003;88:714-715.
[12]Xiao Z,Zhang M,Liu X,et al.MEL Is,not MEL1,is overexpressed in myelodysplastic symdromes patients with t(l;3)(p36;q21).Leuk Res,2006,30:332-334.
[13]Pfeilstocker M,Reisner R,Nosslinger T,et al.Cross-validation of prognostic scores in myelodysplastic syndromes on 386 patients from a single institution confirms importance of cytogenetics.Br J Haematol,1999,106:455-463.
[14]Belli C,Acevedo S,Bengio R,et al.Detection of risk groups in myelodysplastic syndromes.A multicenter study.Haematologica,2002,87:9-16.
[15]Lorand-Metze I,Pinheiro MP,Ribeiro E,et al.Factors influencing survival in myelodysplastic syndromes in a Brazilian population:comparison of FAB and WHO classifications.Leuk Res,2004,28:587-594.
[16]Muller-Berndorff H,Haas PS,Kunzmann R,et al.Comparison of five prognostic scoring systems,the French-American-British (FAB)and World Health Organization (WHO)classifications in patients with myelodysplastic syndromes:results of a single-center analysis.Ann Hematol,2006,85:502-513.
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[1]肖志坚.骨髓增生异常综合征:现况与问题.白血病·淋巴瘤.2005,14:193-196.
[2]郝玉书,肖志坚.骨髓增生异常综合征∥郝玉书,肖志坚,王建祥等.白细胞疾基础与临床.第1版.上海:上海科学技术出版社,2006:428-452.
[3]Baumann Kreuziger LM,Steensma DERAD51 and XRCC3 polymorphism frequency and risk of myelodysplastic syndromes.Am J Hematol.2008,83:822-823.
[4]李磷,肖志坚.急性白血病药物基因组学研究现况.中国实验血液学杂志.2008,16:704-711.
[5]Vardiman JW,Harris NL,Brunning RD,et al.The World Health Organization (WHO) classification of the myeloid neoplasms.Blood,2002,100:2292-2302.
[6]杨琳,张美荣,张悦,等.RAD51_(G135C)和XRCC3_(C241T)多态性与急性髓系白血病和骨髓增生异常综合征的发生及其染色体异常相关性研究.中华血液学杂志.2006,27:727-731.
[7]杨琳,邹煦,张美荣,等.骨髓增生异常综合征患者GSTT1、GSTM1基因分布频率和NQO1基因多态性分析.中华血液学杂志.2005,26:674-677.
[8]Fabiani E,D'AI(?) F,Scardocci A,et al.Polymorphisms of detoxification and DNA repair enzymes in myelodyplastic syndromes.Leuk Res.2008 Nov 21.[Epub ahead of print].
[1]郝玉书,肖志坚.骨髓增生异常综合征//郝玉书,肖志坚,王建祥等.白细胞疾病基础与临床.第1版.上海:上海科学技术出版社,2006:428-452.
[2]Bernasconi P,Klersy C,Boni M,et al.World Health Organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes.Br J Haematol,2007,137:193-205
[3]Vardiman JW,Harris NL,Brunning RD,et al.The World Health Organization (WHO) classification of the myeloid neoplasms.Blood,2002,100:2292-2302.
[4]Malcovati L,Germing U,Kuendgen A,et al.A WHO classification-based prognostic scoring system(WPSS) for predicting survival in myelodysplastic syndromes.Blood,2005,106:Abstract 788.
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