Absence of reverse transcription-polymerase chain reaction detectable residual disease in patients with acute promyelocytic leukemia in long- term remission
Absence of reverse transcription-polymerase chain reaction detectable residual disease in patients with acute promyelocytic leukemia in long- term remission
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DOI：
10.1182/blood.v82.12.3556.bloodjournal82123556
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发表时间：
1993-12
期刊：
影响因子：
20.3
通讯作者：
D. Diverio;P. Pandolfi;A. Biondi;G. Avvisati;M. Petti;F. Mandelli;G. Pelicci;F. Coco
中科院分区：
文献类型：
--
作者：
D. Diverio;P. Pandolfi;A. Biondi;G. Avvisati;M. Petti;F. Mandelli;G. Pelicci;F. Coco
杂交融合基因是几种白血病亚型的特异性肿瘤标志物。利用逆转录聚合酶链反应（RT-PCR）来扩增嵌合cdna，可以灵敏地检测肿瘤克隆，用于这些白血病的诊断和监测研究。尽管如此，通过PCR评估微小残留病（MRD）的临床相关性仍然存在争议。本研究通过RT-PCR扩增特异性PML/ rar - α融合基因，分析了9例长期缓解期为4 ~ 12年的急性早幼粒细胞白血病（APL）患者是否存在MRD。7例患者单独接受常规化疗（CHT）， 1例接受同种异体骨髓移植（BMT）， 1例接受自体骨髓移植作为CHT后的巩固治疗。在8例病例中，通过细胞遗传学和/或分子分析可以在诊断性BM标本中证实t（15;17）重排的存在。采用两轮“巢式”RT-PCR检测，灵敏度水平为1 / 10(5)，用于分析在达到完全缓解（CR）后32至141个月收集的BM样本。在这些缓解对照中没有检测到残留的PML/ rar - α转录物。所有患者在CR后48至154个月和PCR评估后6至17个月处于未维持CR。这些结果表明，APL的长期生存与清除携带特异性PML/RAR-alpha重排的细胞有关，表明PCR阴性应被视为这些患者的治疗目标。我们的研究结果进一步加强了APL中PCR监测研究的临床意义，而其他白血病亚型（慢性髓性白血病和急性髓性白血病- m2）的PCR评估预后意义尚不清楚。
Hybrid fusion genes are specific tumor markers of several leukemic subtypes. The use of reverse transcription-polymerase chain reaction (RT-PCR) to amplify chimeric cDNAs allows sensitive detection of the neoplastic clone for diagnostic and monitoring studies in these leukemias. Nonetheless, the clinical relevance of minimal residual disease (MRD) evaluation by PCR remains controversial. In this study, 9 patients (pts) with acute promyelocytic leukemia (APL) in long-term remission for 4 to 12 years were analyzed for the presence of MRD by RT-PCR amplification of the specific PML/RAR-alpha fusion gene. Seven pts had been treated with conventional chemotherapy (CHT) alone, 1 had undergone allogeneic bone marrow transplantation (BMT), and 1 autologous BMT as consolidation therapy after CHT. In 8 cases, the presence of the t(15;17) rearrangement could be documented in diagnostic BM specimens by cytogenetic and/or molecular analysis. A two-rounds "nested" RT-PCR assay with sensitivity levels of 1 in 10(5) was used to analyze BM samples collected at 32 to 141 months from the achievement of complete remission (CR). In no cases were residual PML/RAR-alpha transcripts detectable in these remission controls. All patients are in unmaintained CR at 48 to 154 months from CR and at 6 to 17 months from PCR evaluation. These results suggest that long-term survival of APL is associated with eradication of cells carrying the specific PML/RAR-alpha rearrangement, indicating that PCR negativity should be considered the therapeutic goal in these patients. Our findings further strengthen the clinical relevance of PCR monitoring studies in APL, as opposite to other leukemic subtypes (chronic myeloid leukemia and acute myeloid leukemia-M2) in which the prognostic significance of PCR evaluation is unclear.