骨髓增生异常综合征435例WHO分型和细胞遗传学分析

WHO classification and cytogenetic analysis of 435 cases with myelodysplastic syndrome

目的探讨我国骨髓增生异常综合征（MDS）WHO亚型分布和细胞遗传学异常特点，并与西方国家进行比较。方法采用前瞻性方法收集了协作组435例MDS患者，进行WHO分型，采用染色体G显带和荧光原位杂交（FISH）技术进行细胞遗传学分析。结果MDS中位发病年龄为58（18～90）岁。难治性血细胞减少伴多系发育异常（RCMD）病例比例最高，约占69．6％（303／435），其他亚型依次为难治性贫血伴原始细胞增多（RAEB）24．1％（105／435）、难治性贫血（RA）2．3％（10／435）、不能分类MDS（MDS—U）2．3％（10／435）、难治性贫血伴环状铁粒幼细胞增多（RAS）1．2％（5／435）和5q-综合征0．5％（2／435），而西方国家RA、RAS、5q-综合征比例较高，RCMD亚型比例低于中国。11例染色体检查失败，424例染色体检查成功的染色体克隆性异常率为38．7％（164／424），其中RAEB—Ⅰ异常率最高62．5％（25／40），其次RAEB—Ⅱ48．4％（30／62）、RCMD34．5％（102／296）。常见的染色体异常依次为：＋8为12．7％（54／424）、复杂核型为9．0％（38／424）、染色体易位为7．8％（33／424）、-20q为6．6％（28／424）、-7／-7q为5．2％（22／424）、-5／-5q为4．2％（18／424），而国外最常见的是-5／-5q、-7／-7q、＋8、11q及120／12q异常。以国际预后积分系统染色体预后分组，染色体预后良好组68．2％（289／424），预后中等组19．1％（81／424），预后不良组12．7％（54／424）。有17例患者因为异常细胞的比例偏低，染色体检查正常，但FISH检测到低水平的异常。结论我国MDS的WHO亚型分布与染色体异常分布与西方国家不同。FISH和常规染色体检查相结合，可以提高检测的灵敏度。

Objective To investigate the WHO classification and cytogenetic characteristics of primary myelodysplastic syndrome （MDS） in adults of Shanghai area and then compare them with those of western countries. Methods The consecutive samples of 435 patients with MDS in Sino-US Shanghai Leukemia Cooperative Group were collected prospectively and diagnosed with WHO classification. Cytogenetic analysis was performed using chromosome G-banding and fluorescence in situ hybridization （FISH） techniques. Results The median onset age in the patients was 58 （ 18 -90） years. The proportion of cases with refractory cytopenia with multilineage dysplasia （RCMD） was highest , accounting for 69. 6% （303/435）. Other subtypes were refractory anemia with excess blasts （RAEB） 24. 1% （ 105/435 ）, refractory anemia （RA） 2. 3% （ 10/435 ）, myelodysplastic syndrome, unclassifiable （MDS-U） 2. 3% （10/435） ,refractory anemia with ringed sideroblasts （RAS） 1.2% （ 5/435 ） and 5q-syndrome 0. 5% （2/435） in turn. The proportions of RA, RAS and 5q-syndrome were higher in western countries and RCMD subtype was lower. Eleven cases had failure of chromosome analysis. In the remaining 424 cases with success the frequency of chromosome abnormality was 38. 7%, with the highest in RAEB- Ⅰ （62.5%） , and then RAEB- Ⅱ （ 48.4% ） and RCMD （ 34. 5% ） in turn. The sequence of common chromosome abnormalities was ＋ 8 （ 12. 7% ）, complex karyotype （9. 0% ）, chromosome translocation （7. 8% ）, - 20q （6.6%）, -7/-7q （5. 2% ）, -5/-Sq （4. 2% ） and -Y（2. 4% ）, while the sequential order in western countries - 5/- 5q, - 7/- 7q, ＋ 8, 11 q and 12p/12q. Chromosome prognosis was grouped according to International Prognosis Scoring System （IPSS）, 289 cases were in the group with good chromosome prognosis （68. 2% ） , 81 cases in group with medium prognosis （ 19. 1% ） and 54 cases in group with poor prognosis （ 12.7% ）. Seventeen patients had normal chromosome examination because of lower percentage of abnormal cells. However, the detection sensitivity of abnormality with FISH may sometimes be high. Conclusions The WHO subtype and chromosome abnormality distributions of MDS in Shanghai were different from those in western countries. The combination of FISH and conventional chromosome examination could improve the detection sensitivity.