染色体核型分析和荧光原位杂交技术监测慢性髓性白血病患者细胞遗传学反应的比较  

Comparative study of cytogenetic response evaluated by conventional banding analysis and fluorescence in situ hybridization in chronic myeloid leukemia patients during tyrosine kinase inhibitor treatment

作　　者：王峥[1] 李娜[1] 高露[1] 冯麟[1] 秦亚溱[1] 党辉[1] 师岩[1] 何琦[1] 江倩[1] 江浩[1] 赖悦云[1] 

机构地区：[1]北京大学人民医院、北京大学血液病研究所,造血干细胞移植治疗血液病北京市重点实验室,100044

出　　处：《中华血液学杂志》2017年第11期962-967,共6页Chinese Journal of Hematology

摘　　要：目的比较染色体核型分析和荧光原位杂交（FISH）两种方法检测酪氨酸激酶抑制剂（TKI）治疗慢性髓性白血病（CML）细胞遗传学反应的差异，及其与分子学反应的相关性。方法同期采集367例CML患者504份骨髓样本，以传统显带分析（CBA）法和FISH法进行染色体分析，以实时荧光定量PCR（RQ．PCR）法检测BCR-ABL转录本水平。结果504份样本中，采用CBA法检测，344份达完全细胞遗传学反应（CCyR）；采用FISH法检测，297份达CCyR（BCR-ABL＋细胞〈1％）。同期比较493份标本的CBA、FISH和RQ—PCR结果，在337份CBA—CCyR的样本中，273份（81．0％）达FISH．CCyR，289份（85．8％）分子学反应BCR-ABL1s≤1％；290份FISH—CCyR样本中，261份（90．0％）分子学反应BCR—ABL1s≤1％。CBA．CCyR和FISH．CCyRIN组样本BCR-ABL1s中位数分别为0．21％和0．13％，差异无统计学意义（z=-1．875，P=0．061）。将FISH结果按BCR-ABL＋细胞比例分成0、〉0-〈1％、1％～5％;组，二三组样本获分子学反应BCR-AB1s≤1％的比例分别为94．1％、57．6％、27．7％，差异有统计学意义（z=43．499，P〈0．001；#=9．734，P=0．003）；三组BCR-ABL1s中位数分别为0．10％、0．64％、1．80％，差异有统计学意义（z=-5．864，P〈0．001；z=-4．787，P〈0．001）。结论CBA和FISH两种方法对于CCyR的监测具有较好的一致性，FISH比CBA法敏感性更高，FISH结果与分子学反应有更好的一致性，但如何定义FISH．CCyR仍需大宗病例随访研究。Objective To compare the cytogenetic response detected by conventional banding analysis （CBA） and fluorescence in situ hybridization （FISH） and to explore the correlation between the cytogenetic and molecular response in chronic myeloid leukemia （CML） patients during tyrosine kinase inhibitor （TKI） treatment. Methods CBA, FISH and real-time quantitative reverse transcriptase polymerase chain reaction （RQ-PCR） methods were performed to detect the cytogenetic and molecular response simultaneously in 504 bone marrow samples from 367 CML patients who received TKI treatment. Results Among 504 samples, 344 were detected to reach complete cytogenetic response （CCyR） by CBA, while 297 samples reached CCyR by FISH which were considered to carry BCR-ABL positive cells 〈 1%. When the results of CBA, FISH and RQ-PCR were compared in 493 samples at the same time, it showed that in 337 samples with CBA-CCyR, 273 （81.0%） reached FISH-CCyR and 289 （85.8%） were BCR-ABL^s （International Scale, IS） ≤1% by RQ-PCR, compared to 9.0 （261/290） were BCR-ABL1s ≤1% among 290 samples with FISH-CCyR. There was no significant difference in the median value of BCR- ABLjs between samples in CBA- CCyR and FISH- CCyR （0.21% vs 0.13%, z=-1.875, P=0.061）.Furthermore, when the samples were divided into three groups according to BCR-ABL positive cells （0, 〉 0 - 〈 1%, 1% ~ 5% ） by FISH, the statistical difference was observed, the proportion of samples with BCR- ABL1s≤1% in the three groups were 94.1%, 57.6% and 27.7% respectively （z2 = 43.499, P 〈 0.001; 2（ = 9.734, P = 0.003 ）, while the median value of BCR-ABL1s were 0.10%, 0.64% and 1.80% respectively （z = - 5.864, P 〈 0.001; z = -4.787, P 〈 0.001 ）. Conclusion FISH results were in good concordance with CBA in identify samples in CCyR, FISH was more sensitive and had better correlation with RQ-PCR results than CBA, but how to define FISH-CCyR need further study.

关 键 词：白血病 髓系 慢性 BCR-ABL阳性 细胞遗传学分析 原位杂交 荧光 

分 类 号：R733.72[医药卫生—肿瘤]