北京地区长寿老人细胞遗传学研究

本文对30例95岁以上老人(长寿组)和30例中年人(对照组)细胞遗传学进行比较研究。结果表明,染色单体畸变率、姐妹染色单体互换(SCE)频率和亚二倍体细胞百分率长寿组均明显高于对照组(分别为2.3VS1.56/每100个细胞、5.3±1.5/细胞 VS 4.1±0.6/细胞和8.88％VS 6.78％,P<0.05),认为上述指标可作为衰老指标。而有丝分裂指数(6.85％VS 6.56％,P>0.05)两组无显著差异,说明长寿老人的细胞还能保持相当的分裂能力。加松胞素 B(CB)后双核细胞微核率两组差异不显著(15.2‰VS13.9‰,P>0.05),其意义尚需进一步研究。     

急性早幼粒细胞白血病细胞形态学与基因异质性关系的研究

经形态学诊断为急性早幼粒细胞白血病（ＡＰＬ）的５０例患者进行了细胞遗传学、分子生物学以及用全反式维甲酸（ＡＴＲＡ）治疗反应的观察，其中４５例有典型的染色体易位ｔ（１５；１７）及早幼粒细胞白血病基因／维甲酸受体α（ＰＭＬ／ＲＡＲα）融合基因（ＰＭＬ＋ＲＡＲα＋型ＡＰＬ），用ＡＴＲＡ治疗有显效；另有三种基因异质型，分别为早幼粒细胞锌指蛋白基因（ＰＬＺＦ）＋ＲＡＲα＋型ＡＰＬ、ＰＭＬ－ＲＡＲα＋型ＡＰＬ和ＰＭＬ－ＲＡＲα－型ＡＰＬ，对ＡＴＲＡ治疗均无反应。由此可见，ＡＰＬ是一种不均一性疾病。其余２例经形态学仔细复核分别实属Ｍ＿２α和Ｍ＿５ｂ，用ＡＴＲＡ治疗前者有效，后者无效。形态学是确诊ＡＰＬ的重要依据，少数患者应依赖细胞遗传学甚至分子生物学肯定诊断。ＡＴＲＡ治疗的反应可对ＡＰＬ诊断有重要参考价值，但非ＡＰＬ的特异诊断标准。     

977例异常孕产史夫妇的染色体核型分析

目的:探讨异常孕产史夫妇与染色体核型异常的关系。方法:对977例异常孕产史夫妇进行外周血淋巴细胞培养及染色体核型分析。结果:染色体异常核型52例,染色体异常率为5.32%,其中,平衡异位26例,倒位13例,多态性变异11例,分别占染色体异常核型的50%、25%和21.2%。结论:染色体核型异常是导致异常孕产史的重要原因之一,对异常孕产史夫妇进行细胞遗传学检查十分必要。     

湛江地区207例先天愚型的染色体分析

对湛江地区２０７例先天愚型进行了染色体分析，标准２１三体型占８８．４１％，易位型占３．８６％，嵌合型占６．７６％，伴有其它染色体异常者占０．９７％。对易位型和伴有其它染色体异常者作了家系分析。对先天愚型的细胞遗传学病因及先天愚型患病率的性别差异问题作了讨论     

Cytogenetic remission with imatinib therapy in hypereosinophilic syndrome with trisomy 8 and resolution of severe cardiac dysfunction

We report a 50-year-old patient with idiopathic hypereosinophilic syndrome with trisomy 8 who experienced a complete and durable hematological and cytogenetic remission with low-dose imatinib therapy. He also had a significant reversal of cardiac dysfunction with a reduction in cardiac hypertrophy, resolution of pericardial effusion and mitral and tricuspid regurgitation. He remained in remission 3 years after therapy.     

Cytogenetic analysis of 52 Indian patients with de novo myelodysplastic syndromes—a comparative analysis of results with reports from Asia

Most published data on myelodysplastic syndromes (MDS) are derived from Western countries, which report MDS as a disease of the elderly. However, it was observed that Asian MDS patients were younger than subjects in Western reports. With this in mind, the study was conducted prospectively on 52 Indian patients to define chromosomal abnormalities and to understand ethno-geographical differences, if any, underlying the pathogenesis of MDS among this Asian population. Cytogenetic analysis was performed using GTG banding and karyotyped according to the International System for Human Cytogenetic Nomenclature (ISCN). The incidence of MDS was predominant in the age group of 41–60 years (44.23%), with a median age at diagnosis of 55 years. The disease was more frequent in males (33 patients, 63.46%) than females (19 patients, 36.53%). Of 48 patients successfully karyotyped, 17 had normal karyotype (35.4%) and 31 patients (64.5%) had a chromosomal abnormality. The most frequent chromosome abnormalities were del 5q/–5 in 13 patients (42%), –7/7q– in 10 patients (32.2%), +8 and del 20q– in 6 cases each (19.3%) and i(17)(q10) in 1 patient (3.2%). In addition to these non-random chromosomal abnormalities, some rare abnormalities were also encountered. A higher rate of transformation to acute myeloid leukaemia (AML) was observed in the Chinese population compared to other Asian countries. The incidence of chromosomal abnormalities varied considerably across the different Asian populations. The overall frequency of chromosomal abnormalities in our study was comparable to most Western reports. Further prospective studies are warranted to elucidate precisely the ethnic differences in the pathogenesis of MDS in the Indian population.     

Cytogenetic analysis of the spontaneous murine B-cell leukemia (BCL1

Cytogenetic studies were carried out on the spontaneous transplantable murine B cell leukemia (BCL₁) of BALB/c mice, a recently discovered model of chronic lympholytic leukemia. BCL₁ tumor cells appear as medium to large size mature lymphocytes located predominantly in the blood (up to 500,000/mm³) and in the x50 enlarged spleen. BCL₁ cells obtained from the spleen show a certain degree of spontaneous proliferation unlike peripheral blood lymphocytes (PBL), but both show a good in vitro response to the B-cell mitogen lipopolysaccharide (LPS). Out of 213 spontaneously dividing spleen cells and LPS stimulated PBL studied, the majority (75.5%) showed a rather stable and complex female karyotype consisting of 36 chromosomes. No normal representative of chromosome Nos. 6, 8, 12 and 15 was present and only one normal representative was found for chromosome Nos. 4, 5, 9, 14 and X. Two deleted chromosomes and seven characteristic marker chromosomes, originating from complex chromosomal rearrangements could be identified in each cell. Of special interest was the t(12:15) translocation, which had been found in several murine plasmacytomas. No direct correlation between the chromosomal changes and the phenotypic characteristics of BCL₁ tumor cells could be made. However, the highly specific karyotype may serve as a useful marker in identifying single BCL₁ tumor cells.     

Nonclonal neutrophil responses after successful treatment of myelodysplasia with low-dose 5-aza-2'-deoxycytidine (decitabine)

The demethylating agents 5-aza-2′-deoxycytidine (decitabine, DAC) and 5-azacytidine at low doses induce hematologic and cytogenetic remissions in a subset of patients with MDS. It is unclear whether the correction of neutropenia involves differentiation of abnormal granulocyte precursors, or emergence of normal granulopoiesis. A previous study in three MDS patients, analyzing a differentiating activity of GM-CSF, had shown heterogenous granulocyte responses. The objective of our study was to determine the ratio of clonal and nonclonal peripheral blood granulocytes in MDS patients treated with DAC using FISH analysis. In two patients with initial severe neutropenia, an informative cytogenetic marker, complete normalization of peripheral blood neutrophils and a bone marrow cytogenetic response following DAC, >90% of the cells contributing to neutrophil normalization lacked this clonal marker. In one of them, an early and transient increase in clonal neutrophils was compatible also with a modest differentiating effect upon the dysplastic granulocyte precursors, whereas in a third patient, resistant to re-treatment with DAC, no expansion of either granulocyte population occurred. In the responders, leukocyte nadirs following DAC appeared less pronounced after conversion to normal cytogenetics. In conclusion, restoration of nonclonal hematopoiesis may be the predominant effect of DAC both in early and late stages of treatment, at least in patients achieving a hematologic and cytogenetic response.     

Tissue sampling technique affects accuracy of karyotype from missed abortions

Purpose : To determine if careful specimen selection and washing of tissue from first trimester missed abortion products of conception specimens increases the sensitivity of routine cytogenetics in detecting aneuploidy. Methods : Retrospective review of cytogenetics results from tissue from dilation and curettage for missed abortion in a university fertility practice between 1998 and 2001. A technique of careful selection and washing of the specimen was implemented in July 1999. Results from before (n = 15) and after (n = 41) this change were compared. Cytogenetics reports from other physicians using the same laboratory were used for comparison (n = 59). Results : The percentage of 46XX results was significantly decreased in the test group when compared to historical and community controls: 29% vs. 73% and 56% respectively. The percentage of aneuploid results was significantly higher in the test group at 61% vs. 7% and 36% in the historical and community controls respectively. Conclusion : Thorough separation and cleaning of villi prior to sending missed abortion specimens significantly increases sensitivity of conventional cytogenetics for detecting aneuploidy by decreasing maternal contamination.