原发性骨髓增生异常综合征染色体核型异常特征及其预后意义的研究

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及其预后意义.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%)的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、RCMD-RS组,RAEB-Ⅰ组,RAEB-Ⅱ组依次升高,差异有统计学意义(X2=2.854,P＜0.01).351例MDS患者中,177例获得随访资料,中位随访时间14.5(1～131)个月,81例死亡,中位生存期(MS)12(1～90)个月.按IPSS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51[95%可信区间(CI)25～77]、35(95%CI 5～65)和13(95%CI 9～17)个月,Log-rank检验三组总体生存(OS)率差异有统计学意义(P=0.004).染色体核型按正常核型(NN)、嵌合核型(AN)、异常核型(AA)分组,NN、AN、从患者MS分别为51(95%CI 24～78)、36(95%CI 0.3～71)和23(95%CI 10～35)个月,Log-rank检验三组OS率差异有统计学意义(P=0.039).结论 我国MDS患者具有有别于两方国家MDS患者的染色体核型异常特征.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.

Study on karyotypic abnormalities and its prognostic significance in Chinese patients with primary myelodysplastic syndromes

Objective To investigate the features and prognostic significance of chromosomal karyotype in patients with primary myelodysplastie syndromes(MDS).Methods Results of chromosomal karyotypes of 351 adult patients with primary MDS were retrospectively analyzed.Results Two hundred and thirty-seven cases(67.5%)had karyotypic abnormalities.Of them,99(41.7%)were numerical,70(29.5%)were structural,and 68(28.8%)were complex abnormalities.In addition,among the 237 patients with chromosomal abnormalities,130(54.8%)showed single abnormality,54(22.8%)double abnormalities and 53(22.4%)complex abnormalities(≥3 two independent aberrations).Four eases(1.7%)wero muhiploid.Aneuploidy or of chromosomal arm anomaly were detected all of the 46 chromosomes and the aberrations in frequent order wero+8,-20/20q-,-7/7q-,-5/5q-,-18,-11/11q-/,+21,-Y,-21,-10,-16,-22,+9,del(12)(p12).The incidence of-5/5q-(5.1%)wag lower in our series thanin western countries(8.7%-23.4%)and 5q-syndrome waft even less(0.3%).The incidences of+8 (19.1%)and-20/20q-(9.4%)were higher in our series than in western countries(1.2%-7.0%,2.0%-3.5%.respectively).Chromosome translocations were detected in 3l cases(13.1%),including 12novel translocations that have not been reported in MDS patients before.In addition,i(17)(q10)Was detected in 9 cases(3.8%)of which 6 were simplex anormality.Chromosomal duplication presented in 7 cases(3.0%)with 4 cases involved chromosome 1.According to IPsS chromosomal prognositic classification,the incidence of poor-risk karyotypes was increased in the advanced WHO subtypes(P＜0.001).The follow-up data were available in 177 patients with a median follow-up duration of 14.5(1-131)months.The median OS Was 36[95%confident interval(CI)25-46]months.According to IPSS chromosomal prognostic classification,the median OS of patients with good,intermediate and poor-risk cytogenetie subgroup were 51(95%CI 25-77),35(95%CI 5-65)and 13(95%CI 9-17)months,respectively(P=0.004)and for NN-ANAA karyotype classification,the median OS of NN,AN and AA were 51(95%CI 24-78),36(95%CI 0.3-71)and 23(95%CI 10-35)months,respectively(P=0.039).Conclusion The features of chromosomal abnormalities in Chinese patients with primary MDS shows some difierence from that in western countries.Karyotype analysis is of great importance to predict prognosis and to tailor individualized therapy forMDS.