多重荧光原位杂交检测慢性粒细胞白血病急变期复杂核型异常

Multiplex fluorescence in situ hybridization for detecting complex chromosomal aberrations in chronic myeloid leukemia in blast crisis

目的探讨多重荧光原位杂交(M-FISH)技术检测慢性粒细胞白血病急变期(CML-BC)复杂核型异常(CCA)的价值。方法应用 M-FISH 技术对26例常规细胞遗传学(CC)分析显示 CCA的 CML-BC 患者进行检测分析。结果除标准 t(9;22)(q34;q11)外,通过 M-FISH 技术共检出69种结构异常,其中10种为平衡易位,59种为不平衡易位,不平衡易位包括1种插入、6种缺失及52种易位及衍生染色体;另外还检出23种数目异常。26例 CML-BC 患者中所有染色体均涉及异常,除标准t(9;22)外异常最多涉及的染色体是17号、2号、8号及16号。1例标本 M-FISH 未检出 CCA,6例标本检出了 CC 分析未发现的异常核型。M-FISH 明确了16种 CC 分析未确定的异常,纠正了5种 CC 分析识别错误的异常,还发现了 CC 分析未检出的35种染色体易位,其中 der(9)t(16;6;9;22)和 der(18)t(16;18;19)在既往文献中未见报道。结论对伴有 CCA 的 CML-BC 以 M-FISH 技术可以发现和纠正CC 分析漏检及误检的染色体异常。伴有 CCA 的 CML-BC 与 CML 常见的附加异常不同。

Objective To investigate the value of multiplex fluorescence in situ hybridization （ MFISH） for the detection of complex chromosomal abnormalities （CCA） of chronic myeloid leukemia in blast crisis （CML-BC）. Methods M-FISH was used to study 26 cases of CML-BC with CCA assayed by conventional cytogenetics （CC）. Results Sixty-nine kinds of structural rearrangements were detected by M-FISH besides typical t（9 ;22 ） translocation, among them only 10 were balanced ones and 59 unbalanced ones inclu- ding 1 insertion, 6 deletions, 52 translocations and derivative chromosomes. In addition, 23 numerical abnormalities were detected. All chromosomes were involved in CML-BC, and chromosomes 17, 2, 8, 16 involvements were the most frequent. M-FISH failed to find out the abnormal clone in 1 case, discovered CCA clones that were missed CC in 6 cases. Clarified 16 kinds of aberrations which could not be identified CC and corrected 5 aberrations made wrong description by CC. Thirty-five kinds of translocations were found by M-FISH which were missed by CC. The aberrations of der（9） t（ 16;6;9 ;22） and der（18） t（ 16; 18; 19） we found were reported in the literature for the first time. Conclusions M-FISH can refine CCA in CML-BC, find out or correct the missed or misidentified abnormalities by CC. The frequent secondary chromosomal abnormalities in CML-BC with CCA are different from that in CML.