Design and validation of DNA probe sets for a comprehensive interphase cytogenetic analysis of acute myeloid leukemia
Design and validation of DNA probe sets for a comprehensive interphase cytogenetic analysis of acute myeloid leukemia
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DOI：
10.1182/blood.v88.10.3962.bloodjournal88103962
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发表时间：
1996-11-15
期刊：
影响因子：
20.3
通讯作者：
Dohner, H
中科院分区：
文献类型：
--
作者：
Fischer, K;Scholl, C;Dohner, H
本研究的目的是设计DNA探针组，通过荧光原位杂交（FISH）通过间期细胞遗传学检测急性髓系白血病（AML）的染色体畸变，并将间期细胞遗传学的结果与常规染色体显带分析的结果进行比较。对105例连续入组多中心治疗试验的成人AML患者进行了研究，使用了一套全面的DNA探针识别最相关的AML相关染色体结构和数目畸变：易位t（8;21），t（15;17）和t（11 q23）;倒位inv（16）;染色体缺失（5 q-、7 q-、9 q-、12 p-、13 q-、17 p-和20 q-）;和染色体非整倍性。间期细胞遗传学对检测AML特异性基因融合特别敏感：FISH鉴定了3例inv（ls）和1例t（8;21），但条带分析未发现，而检测到相同数量的ok t（11 q23）和t（15;17）。FISH结果显示8 q三体5例，11 q三体3例，21 q和22 q三体2例。这些畸变在复杂的核型中被掩盖，或者在常规显带分析失败的情况下被识别。另一方面，所选择的DNA探针对1例5 q-、9 q-和20 q-缺陷没有提供信息。在5例病例中，未选择FISH探针的显带分析发现克隆畸变。总之，间期细胞遗传学被证明是更敏感的检测AML特异性嵌合基因融合和一些部分三体。间期细胞遗传学提供了一个强大的技术互补，并与诊断DNA探针的进一步发展，甚至替代染色体显带研究AML的细胞遗传学分析。(C)1996年，美国血液学会。
The objective of this study was to design DNA probe sets that enable the detection of chromosome aberrations in acute myeloid leukemia (AML) by interphase cytogenetics using fluorescence in situ hybridization (FISH) and to compare the results of interphase cytogenetics with those of conventional chromosome banding analysis. One hundred five consecutive patients with adult AML entered on a multicenter treatment trial were studied with a comprehensive set of DNA probes recognizing the most relevant AML-associated structural and numerical chromosome aberrations: translocations t(8;21), t(15;17), and t(11q23); inversion inv(16); chromosomal deletions (5q-, 7q-, 9q-, 12p-, 13q-, 17p-, and 20q-); and chromosomal aneuploidies. Interphase cytogenetics was particularly sensitive for detecting the AML-specific gene fusions: 3 additional cases of inv(ls) and 1 additional case of t(8;21) were identified by FISH that were missed by banding analysis, whereas equal numbers ok t(11q23) and t(15;17) were detected. Five additional cases of trisomy 8q, 3 more cases of trisomy 11q, and 2 more cases of trisomies 21q and 22q were shown by FISH. These aberrations were either masked in complex karyotypes or identified in cases in which conventional banding analysis failed. On the other hand, the DNA probes selected were not informative to defect 1 case of 5q-, 9q-, and 20q-. In 5 cases, clonal aberrations were defected on banding analysis for which no FISH probes were selected. In conclusion, interphase cytogenetics proved to be more sensitive for detecting AML-specific chimeric gene fusions and some partial trisomies. Interphase cytogenetics provides a powerful technique complementary and, with further development of diagnostic DNA probes, even an alternative to chromosome banding studies for the cytogenetic analysis of AML. (C) 1996 by The American Society of Hematology.