Kern Wolfgang, Schoch Claudia, Haferlach Torsten, Schnittger Susanne
Laboratory for Leukemia Diagnostics, Ludwig-Maximilians-University, University Hospital Grosshadern, Department of Internal Medicine III, 81366 Muenchen, Germany.
Crit Rev Oncol Hematol. 2005 Nov;56(2):283-309. doi: 10.1016/j.critrevonc.2004.06.004. Epub 2005 Oct 5.
Monitoring minimal residual disease (MRD) becomes increasingly important in the risk-adapted management of patients with acute myeloid leukemia (AML). The two most sensitive and quantitative methods for MRD detection are multiparameter flow cytometry (MFC) and real-time polymerase chain reaction (QRT-PCR). Fusion gene-specific PCR in AML is based on the RNA level, and thus in contrast to MFC expression levels rather than cell counts are assessed. For both methods independent prognostic values have been shown. The strong power of MFC has been shown mainly in the assessment of early clearance of the malignant clone. MRD levels in AML with fusion genes have the strongest prognostic power after the end of consolidation therapy. In addition, with QRT-PCR highly predictive initial expression levels can be assessed. With both methods early detection of relapse is possible. So far, validated PCR-based MRD was done with fusion genes that are detectable in only 20-25% of all AML MFC is superior since it is applicable for most AML. However, QRT-PCR is still more sensitive in most cases. Thus, it is desirable to establish new molecular markers for PCR-based studies. Large clinical trials will determine the role and place of immunologic and PCR-based monitoring in the prognostic stratification of patients with AML.
监测微小残留病(MRD)在急性髓系白血病(AML)患者的风险适应性管理中变得越来越重要。检测MRD的两种最敏感且定量的方法是多参数流式细胞术(MFC)和实时聚合酶链反应(QRT-PCR)。AML中融合基因特异性PCR基于RNA水平,因此与MFC相反,评估的是表达水平而非细胞计数。两种方法均已显示出独立的预后价值。MFC的强大作用主要体现在对恶性克隆早期清除的评估中。融合基因阳性的AML患者在巩固治疗结束后,MRD水平具有最强的预后价值。此外,通过QRT-PCR可以评估具有高度预测性的初始表达水平。两种方法都可以早期检测复发。到目前为止,基于PCR的MRD验证是针对仅在20%-25%的所有AML中可检测到的融合基因进行的,MFC更具优势,因为它适用于大多数AML。然而,在大多数情况下QRT-PCR仍然更敏感。因此,需要建立新的分子标志物用于基于PCR的研究。大型临床试验将确定免疫监测和基于PCR的监测在AML患者预后分层中的作用和地位。