Department of Haematology, Aarhus University Hospital, Denmark.
Blood. 2011 Mar 3;117(9):2577-84. doi: 10.1182/blood-2010-09-303685. Epub 2010 Nov 19.
An increasing body of data has demonstrated that the traditional concept of morphologic complete remission in acute myeloid leukemia, in which less than 5% myeloblasts is regarded as a sufficient response criterion, is not biologically sound. Fortunately, the quantitative reverse-transcribed polymerase chain reaction (RT-PCR) method seems to be a promising alternative because of its high degree of preclinical standardization and extreme sensitivity on the background of an accurate day-to-day estimate of sample quality. Widespread implementation of this has, however, to some extent been hampered by the lack of knowledge of how and when to measure minimal residual disease levels and, even more importantly, how to react preemptively on a molecular relapse defined by a PCR reversal. Thus, only few prospective studies have been published to date to clinically validate this assay. Here, we discuss outstanding issues in the clinical implementation of RT-PCR for fusion transcripts, mutated and overexpressed genes in acute myeloid leukemia patients in complete remission, and propose a set of guidelines, which can be used when designing prospective trials aimed at validating the use of RT-PCR as well as for following these patients based on mathematical models for disease recurrence recently developed in our laboratory.
越来越多的数据表明，传统的急性髓系白血病形态学完全缓解概念（其中小于 5% 的原始细胞被认为是足够的反应标准）在生物学上是不合理的。幸运的是，定量逆转录聚合酶链反应 (RT-PCR) 方法似乎是一种很有前途的替代方法，因为它具有高度的临床前标准化，并且在准确估计每天样本质量的背景下具有极高的灵敏度。然而，由于缺乏关于如何以及何时测量微小残留疾病水平的知识，甚至更重要的是，如何对分子复发做出先发制人的反应（定义为 PCR 逆转），这种方法在一定程度上受到了阻碍。因此，迄今为止，只有少数前瞻性研究发表，以临床验证这种检测方法。在这里，我们讨论了在完全缓解的急性髓系白血病患者中融合转录本、突变和过表达基因的 RT-PCR 临床应用中的突出问题，并提出了一套指南，可用于设计旨在验证 RT-PCR 应用的前瞻性试验，以及根据我们实验室最近开发的疾病复发数学模型来监测这些患者。
