骨髓增生异常综合征染色体异常与白血病发展

CHROMOSOME ABNORMALITIES OF BM CELLS IN MYELODYSPLASTIC SYNDROMES AND THEIR LEUKEMIA DEVELOPMENT

目的:探讨在骨髓增生异常基础上白血病发展。方法:骨髓细胞Brdu-SCD细胞周期检测法和R-带染色体核型分析法,在1989年—1998年间对361例MDS (按FAB分类) 、11例回顾性诊断白血病前期(PL)和73例MDS-RCMD(按WHO分类)以及140例AA和PNH骨髓细胞进行分析。并对18例MDS-RCMD进行V-erbB基因诊断。还对30例MDS和AA进行动态观察。与此同时,有25例MDS转变为急性白血病,它们几乎都是骨髓细胞SCD阴性患者,与回顾性诊断白前的结果相同。结果:1)361例MDS中MDS-RA占91.3 %,核型异常检出率为66.2 %,SCD阴性病例占50.9 %,与以往报道的结果相似。染色体异常检出率高于文献报道。MDS中两项均不正常的病例占31.5 %。2)AA和PNH核型异常检出率为13.5 %,SCD阴性病例占19.2 %。两项指标均明显低于MDS,且两项均不正常患者仅为1.4 %。3)MDS,RCMD,AA和回顾性白前有相同染色体异常,但有不同的克隆性异常检出率。4)MDS从SCD阳性转变为阴性,AA保持阳性或阴性转变为阳性。结论:1)白前和MDS发展为白血病,或白前转变为MDS而后发展为白血病的共同机制在于骨髓细胞SCD阴性.。它可能与胸苷酸代谢异常和胸苷酸合成酶基因扩增并长期积累有关。2)白前、MDS 和AA 可能有共同的细胞克隆起源。这一点已为AA/AML家系研究所证实。

Objective: To study leukemia development following myelodysplasia in MDS. Methods: Both cytogenetic techniques, Brdu- SCD (sister chromatid differentiation)assay and R- banding karyotypic analysis,in 1989- 1998 the bone marrow(BM)cell chromosomes were analysed in 361 MDS (FAB classification),11 retro- diagnosed(RD) preleukemia and 73 MDS- RCMD (WHO classification ),including 18 ones that were diagnosed by V- erbB gene diagnosis technique.140 AA and PNH were served as control.Among them 30 MDS and AA were followed up and examinated.During the observations 25 MDS had transformed into AL.They all but one are SCD negative,just like RD- preleukemia,which all are SCD negative. Results: The chromosome analysis results were following: 1) In MDS the percentage of patients with karyotypic alterations was 66% and higher than those of literatures,while the percentage of patients with SCD negative was 50.9 % and similar to reported one previously.The percentage of patients with both karyotypic alterations and SCD negative was 31.5 %. 2) In AA and PNH the percentage of patients with karyotypic alterations was only 13.5 %.Besides this, 10 % of patients have unclonal karyotypic alterations.Both patients have the kinds of karyotypic alterations as same as those of MDS.The percentage of patients with SCD negative and with karyotypic alterations /SCD negative was 19.2 % and only 1.4 %, respectively. 3) In MDS,AA and preleukemia(PL)including the retro- or gene diagnosed ones there are common kinds of clonal karyotypic alterations (+8,20q-,-5/5q-,-7/7q-,NCL and Mar). 4) In the 10 years period of following up the results showed that the conversion of SCD positive MDS into negative ones ,while the conversion of SCD negative AA into positive or it still kept SCD positive. Conclusions: 1) the common mechanism of malignant transformation of PL into AL or into MDS and then into AL was of BM cell SCD negative. It may be related to abnormal metabolism of thymidylate,over expression of thymidylate synthase(TS) gene and its accumulation. 2) PL, MDS and AA may have common cell clonal origin that was proved in studies on a AA/AML family.