采用DCDF-FISH早期监测BCR/ABL(+)ALL患者耐药

Early Monitoring Drug-Resistance of Patients with BCR/ABL(+) ALL by DCDF-FISH

本研究探讨双色双融合荧光原位杂交技术(DCDF-FISH)对BCR/ABL阳性伴复杂染色体易位的急性淋巴细胞白血病(ALL)患者的应用价值。通过骨髓细胞形态学检查、染色体分析、流式细胞术和DCDF-FISH技术等方法观察1例急性淋巴细胞白血病的临床特征,并通过DCDF-FISH技术动态观察患者对治疗的反应及病情演变。结果表明:患者发病时呈现急性淋巴细胞白血病表现,流式细胞术发现患者表达幼稚B淋巴细胞分子标志CD10、CD19和CD34,染色体分析显示,患者骨髓细胞有46,XY,i(8),ider(9)t(9;22)[23]/47,idem,+der(22)t(9;22)[7]核型;FISH显示,患者初发病时83%细胞含有BCR/ABL融合基因,其中5%的肿瘤细胞显示1R1G2F信号模式、14%显示1R1G3F、64%显示1R1G4F;患者经格列卫联合VTLP化疗而完全缓解时,FISH显示肿瘤细胞降19%,但是1R1G2F信号模式的细胞却增加到18%;患者经过巩固治疗后复发,1R1G2F信号模式的细胞增加到38%,最后患者因耐药而死亡。结论:复杂易位的BCR/ABL(+)的急性淋巴细胞白血病患者存在多个肿瘤细胞亚群,且不同的亚群对药物的反应性可能不同,因此通过DCDF-FISH技术的信号模式以及对不同亚群细胞动态变化观察,可以在早期监测患者对治疗的反应性以及耐药情况。

This study was aimed to investigate the application value of the dual color dual fusion fluorescence in situ hybridization （DCDF-FISH） in BCR/ABL （＋） acute lymphoblastic leukemia patients with complex chromosomal translocation.The clinical presentations of a patient with ALL were monitored regularly by bone marrow cell morphology test,chromosome analysis,flow cytometry and DCDF-FISH technique,and the reaction of patients to treatment and disease progression were dynamically observed by DCDF-FISH.The results indicated that the patient showed the typical presentation of B lineage acute lymphoblastic leukemia （B-ALL） with expression of CD10,CD19 and CD34; the chromosome analysis showed 46,XY,i （8）,ider （9） t （9 ; 22） [23]/47,idem,＋ der （22） t （9 ; 22） [7] karyotype in the bone marrow cells,FISH showed that 83％ cells contained BCR/ABL fusion gene in the patient＇s bone marrow,among which 5％ cells showed 1R1G2F signalling model,14％ cells showed 1R1G3F,and 64％ cells showed 1R1G4F.The patient got complete remission when the imatinib chemotherapy combined with VTLP was carried out,and the tumor cells decreased to 19％,but the cells with 1R1G2F signal model increased to 18％.The 1R1G2F cell signal model increased up to 38％ when patient relapsed.The patient died of the drug-resistance.It is concluded that the BCR/ABL （＋） leukemia patient with complex translocation has multiple tumor cell subsets,and the responses of different cell subsets to the treatment are different,therefore the response to therapy and drug resistance of patient can be monitored early by the signal model of DCDF-FISH and the observation of dynamical changes of different cell subset.