慢性粒细胞白血病患者Ph染色体变异易位的细胞遗传学特征与荧光原位杂交研究

Analysis and Identification of Variant Ph Chromosome Translocation in Patients with Chronic Myelogenous Leukemia by Conventional Cytogenetics and Fluorescence in situ Hybridization

本研究探讨慢性粒细胞白血病 (CML)中变异Ph染色体易位的细胞遗传学特征并比较双色单融合 (DC SF)与双色双融合 (DC DF)bcr abl探针荧光原位杂交技术 (FISH)在变异易位CML中的应用价值。应用常规细胞遗传学方法分析我院 4 2例CML变异Ph易位患者 ,其中 9例进行DC SF FISH和 11例进行DC DF FISH研究。结果表明 :在 6 4 2例Ph阳性CML中变异易位 4 2例 (6 .5 % ) ,简单变异易位 4 2 .9% (18 4 2 ) ,复杂变异易位 5 4 .8%(2 3 4 2 ) ,遮蔽的或隐匿的Ph易位 1例。除 4 ,6号染色体外 ,其余染色体均被累及。 4种类型变异易位分别出现于至少 2个病例中。变异易位伴附加异常 15例 (35 .7% )。FISH检测bcr abl阳性 19例 (95 % ) ,阴性 1例。DC DF FISH显示除 1例患者部分细胞 (8.8% )能检测到abl bcr融合信号外 ,其他患者皆缺乏该融合信号。但在易位后的9号和参与变异易位的另外染色体上分别可以见到abl和bcr基因信号。DC SF FISH不能观察到信号的变异特征。结论 :CML变异Ph易位广泛累及除 9,2 2外其他染色体 ,部分类型属重现性异常 ;FISH检测能给予精确的分子诊断 ,而DC DF FISH可提供直观的、准确的分子变异特征分析。

The objective of this study was to explore the cytogenetic profiles of variant Ph chromosome translocations (VT) in patients with chronic myelogenous leukemia (CML) and to assess the applications of fluorescence in situ hybridization (FISH) technique for analysis of CML patients with variant translocation by using dual color-single fusion signal (DC-SF) and dual color-dual fusion signal (DC-DF) probe. 42 CML patients with VT were studied by conventional cytogenetic analysis (CCA). Among them,nine and eleven cases were analazed by DC-SF-FISH and DC-DF-FISH,respectively. The results showed that 42 out of 643 (6.5%) CML cases received CCA were found to have VT,which were composed of 18 cases of simple VT, 23 of complex VT and one of masked VT. The VT involved all over the chromosomes but No. 4 and 6. Four patterns of them appeared recurrent because each occurred in at least two cases. VT with additional chromosomal aberrations were shown in 35.7% of patients with VT (15/42). 19 of 20 patients who received FISH detection were positive for bcr/abl fusion. DC-DF-FISH analysis revealed absence of abl/bcr fusion signal in all patients but one (8.8%) with abl/bcr positive cells. However,it was not an implication of gene loss but the translocation led to part of bcr retaining on der (9q34) and other part of bcr translocating to involve another chromosome. It was unable to observe variant signal features by DC-SF-FISH analysis. In conclusion,variant Ph translocations in CML involved almost all chromosomes in a varying frequencies and ways except chromosomes 9 and 22,and some of them showed recurrent aberrations. FISH provides accurate molecular diagnosis for CML with VT,while DC-DF-FISH facilitates the assessment of variant signals.