Brockman Stephanie R, Paternoster Sarah F, Ketterling Rhett P, Dewald Gordon W
Division of Laboratory Genetics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Cancer Genet Cytogenet. 2003 Sep;145(2):144-51. doi: 10.1016/s0165-4608(03)00061-x.
We investigated a new fluorescence in situ hybridization (FISH) method to detect PML/RARA fusion and/or anomalies of the RARA gene (alias RARalpha) in interphase nuclei from patients with acute promyelocytic leukemia (APL). This method uses a commercially available product with two different colored fluorescent probes to detect both PML/RARA gene fusion products (double fusion signal or dual-color fluorescence in situ hybridization [D-FISH]). A total of 82 bone marrow specimens were studied, including 30 from normal bone marrow transplant donors, 33 from patients with untreated APL, 14 from patients with treated APL, and 5 from APL patients with known translocation variants or alternate translocations. The signal patterns and percentage of abnormal nuclei were determined in a blinded study on 500 interphase nuclei for each specimen. Based on 25 normal specimens, the normal cutoff was >0.6% and >1.6% for t(15;17) and t(17;var), respectively. The clinical sensitivity for this series of patients was 98% and the clinical specificity was 100%. The results suggest that the new D-FISH probe set can detect all t(15;17)(q22;q21) and all variant forms of this translocation associated with PML and RARA. In addition, this FISH method can detect all alternate translocations involving RARA and not PML. This FISH method can be used both for the accurate diagnosis of APL and to monitor low levels of disease in treated patients.
我们研究了一种新的荧光原位杂交（FISH）方法，用于检测急性早幼粒细胞白血病（APL）患者间期核中的PML/RARA融合和/或RARA基因（别名RARα）异常。该方法使用一种市售产品，带有两种不同颜色的荧光探针，以检测PML/RARA基因融合产物（双融合信号或双色荧光原位杂交 [D-FISH]）。共研究了82份骨髓标本，包括30份来自正常骨髓移植供体、33份来自未经治疗的APL患者、14份来自接受治疗的APL患者以及5份来自已知易位变体或交替易位的APL患者。在一项盲法研究中，对每个标本的500个间期核确定信号模式和异常核的百分比。基于25份正常标本，t(15;17)和t(17;var)的正常临界值分别为>0.6%和>1.6%。该系列患者的临床敏感性为98%，临床特异性为100%。结果表明，新的D-FISH探针组可以检测所有t(15;17)(q22;q21)以及与PML和RARA相关的该易位的所有变体形式。此外，这种FISH方法可以检测所有涉及RARA而非PML的交替易位。这种FISH方法可用于APL的准确诊断以及监测治疗患者的低水平疾病。
