Jurcic J G, Nimer S D, Scheinberg D A, DeBlasio T, Warrell R P, Miller W H
Leukemia, Hematology, and Developmental Chemotherapy Services, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Blood. 2001 Nov 1;98(9):2651-6. doi: 10.1182/blood.v98.9.2651.
The t(15;17) translocation in acute promyelocytic leukemia (APL) yields a PML/RAR-alpha fusion messenger RNA species that can be detected by reverse transcription-polymerase chain reaction (RT-PCR) amplification. Breakpoints within intron 3 of PML produce a short PML/RAR-alpha isoform, whereas breakpoints within intron 6 result in a longer form. Using RT-PCR, serial evaluations were performed on the bone marrow of 82 patients with APL (median follow-up, > 63 months) who received retinoic acid (RA) induction followed by postremission treatment with chemotherapy, RA, and biologic agents. Sixty-four patients attained a clinical complete remission and had at least 2 RT-PCR assays performed after completing therapy. Forty of 47 patients (85%) with newly diagnosed APL who were induced using RA had residual disease detectable by RT-PCR before additional therapy. After 3 cycles of consolidation therapy, residual disease was found in only 4 of 40 evaluable patients (10%). Among newly diagnosed patients who had 2 or more negative RT-PCR assays, only 3 of 41 (7%) had a relapse, whereas all 4 patients (100%) who had 2 or more positive results had a relapse. Among 63 newly diagnosed patients, those who expressed the short isoform appeared to have shorter disease-free and overall survival durations than patients who expressed the long isoform. These data indicate that 2 or more negative RT-PCR assays on bone marrow, performed at least 1 month apart after completing therapy, are strongly associated with long-term remissions. Conversely, a confirmed positive test is highly predictive of relapse.
急性早幼粒细胞白血病（APL）中的t(15;17)易位产生一种PML/RAR-α融合信使核糖核酸（mRNA），可通过逆转录-聚合酶链反应（RT-PCR）扩增检测到。PML第3内含子内的断点产生一种短的PML/RAR-α异构体，而第6内含子内的断点则产生一种较长的形式。使用RT-PCR，对82例接受维甲酸（RA）诱导治疗，随后进行化疗、RA和生物制剂缓解后治疗的APL患者（中位随访时间>63个月）的骨髓进行了系列评估。64例患者达到临床完全缓解，且在完成治疗后至少进行了2次RT-PCR检测。47例初诊APL患者中，40例（85%）接受RA诱导治疗，在接受额外治疗前可通过RT-PCR检测到残留疾病。经过3个周期的巩固治疗后，40例可评估患者中仅4例（10%）发现残留疾病。在初诊患者中，RT-PCR检测2次或以上呈阴性的患者中，4例中有3例（7%）复发，而RT-PCR检测2次或以上呈阳性的所有4例患者（100%）均复发。在63例初诊患者中，表达短异构体的患者的无病生存期和总生存期似乎比表达长异构体的患者短。这些数据表明，在完成治疗后至少间隔1个月对骨髓进行2次或以上阴性RT-PCR检测与长期缓解密切相关。相反，确诊为阳性的检测结果高度高度高度复发的预测性很高。
