伴有隐匿性染色体重排的急性髓系白血病的荧光原位杂交研究

Fluorescence in situ hybridization study of acute myeloid leukemia with cryptic chromosome rearrangements

目的用间期荧光原位杂交（fluorescenceinsituhybridization，FISH）技术检测急性髓系白血病（acutemyeloidleukemia，AML）伴发的隐匿性染色体重排。方法用骨髓细胞直接法和（或）短期培养制备患者染色体，用R显带进行核型分析。应用MLL、CBFl3／MYHll、AMLl／ETO、PML／RARα等FISH探针分别对FAB亚型为M5、M4、M2、M3，而常规细胞遗传学（conventionalcytogenetics，CC）分析未发现典型易位的病例进行FISH检测。结果用AMLl／ET0探针对38例M2-AML进行了检测，共发现4例t（8；21）阳性，其中包括2例典型信号模式，2例插入易位。用PML／RARα探针对9例CC未见t（15；17）易位的M3-AML进行了检测，共发现6例阳性标本，其中2例为典型信号模式，3例为插入易位，1例FISH及多重逆转录-PCR检测未见PML／RARα，RARα探针检测提示RARA基因部分缺失。用CBFl3断裂点分开的双色FISH探针对23例CC分析未见典型inv（16）的M4（包含M4E0）进行了检测，共发现3例阳性，且均为典型信号。用MLL探针对38例CC分析未见11q23重排的M5进行了检测，结果均为阴性。结论间期FISH检测能够发现少数核型正常的AML的隐匿性重排如AMLl／ET0、PML／RARα和CBFβ／MYH11，但对于检出MLL重排似无帮助。

Objective To detect specific chromosome rearrangements in acute myeloid leukemia （AML） using interphase-fluorescence in situ hybridization（FISH）. Methods All cases were studied by R- band karyotypic analysis using direct method and/or short-term culture for chromosomes preparation. Interphase-FISH was performed in 108 cases of AML with M5, M4, M2, M3 subtypes including 103 cases with normal karyotypes, 4 cases with chromosomal abnormalities other than specific chromosomal rearrangements using chromosome translocation probe such as AML1/ETO, PML/RARα, CBFβ/MYH11 and MLL. Results Of 38 cases of M2-AML without t（8;21） on conventional cytogenetics（CC） analysis, 4 cases showed positivity for AML1/ETO fusion transcript, which included 2 cases with typical signal model and 2 with insertion. Of 9 cases of M3-AML without t（15; 17） on CC analysis, 6 showed positivity for PML/RARα fusion transcript including 2 with typical signal model, 3 with insertion, one without PML/ RARα rearrangement on reverse transcription PCR and FISH assay using PML/RARα probe. FISH assay using the RARα dual color, break-apart rearrangement probe indicated a partial deletion of RARα. Of 23 cases with M4 or M4EO-AML without inv（16） on CC analysis, 3 showed positivity for CBFI3/MYHll fusion transcript. Of 38 cases without 11q23 translocation on CC analysis, all cases were negative for MLL rearrangement. Conclusion Interphase-FISH can detect specific chromosome rearrangements such as AML1/ETO, PML/RARα or CBFβ/MYHll in some AML cases with normal karyotype, though it seemed less useful for the detection of MLL rearrangement.