Drexler H G, Borkhardt A, Janssen J W
DSM-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.
Leuk Lymphoma. 1995 Nov;19(5-6):359-80. doi: 10.3109/10428199509112194.
In recent years many chromosomal translocations involved in leukemia and lymphoma have been defined at the molecular level. In addition to advancing the understanding of pathological mechanisms underlying the transformation process, the cloning and sequencing of the genes altered by the translocations have provided new tools for diagnosis and monitoring of patients. In particular, the polymerase chain reaction (PCR) methodology yields rapid, sensitive and accurate diagnostic and prognostic information. As leukemias carrying certain translocations confer a higher risk of treatment failure, it is important to identify accurately all positive cases in order to give appropriate therapy. An important new initiative in the diagnostical setting and anti-leukemic therapy is the early detection of minimal residual disease (MRD). If MRD, implying an increased risk of relapse, is reliably detected during apparent clinical remission, alternative strategies could be applied early while the malignant cell burden is still minimal. The PCR assays are clearly more sensitive than other methods of MRD detection including morphology, immunophenotyping and cytogenetics; treatment failure is first detectable by PCR followed by cytogenetic relapse and finally clinical disease. PCR assays have been most often used in the MRD analysis of follicular lymphoma with t(14;18), chronic myeloid leukemia and acute lymphoblastic leukemia (ALL) with t(9;22), ALL with t(4;11), and acute myeloid leukemia (AML) with t(8;21) or t(15;17). PCR amplification is applicable to any other translocation provided the translocation is highly associated with the malignancy and the breakpoints are sufficiently clustered; a quickly increasing number of such specific molecular markers are now available for PCR assays. PCR still remains an experimental investigation for the detection of covert disease. However, the clinical relevance of MRD detection should be evaluated separately for each type of leukemia as significant prognostic differences between disease entities were found. This review describes the PCR assays available for the detection of leukemia cells with specific chromosomal translocations and summarizes the experience with the application of PCR techniques in monitoring patients during the course of the disease.
近年来，许多与白血病和淋巴瘤相关的染色体易位在分子水平上已得到明确。除了加深对转化过程病理机制的理解外，对因易位而改变的基因进行克隆和测序，为患者的诊断和监测提供了新工具。特别是，聚合酶链反应（PCR）方法可提供快速、灵敏且准确的诊断和预后信息。由于携带某些易位的白血病患者治疗失败风险更高，准确识别所有阳性病例以便给予适当治疗非常重要。在诊断和抗白血病治疗方面，一项重要的新举措是早期检测微小残留病（MRD）。如果在明显的临床缓解期能可靠地检测到意味着复发风险增加的MRD，那么在恶性细胞负荷仍很小时就可尽早应用替代策略。PCR检测显然比其他MRD检测方法更灵敏，包括形态学、免疫表型分析和细胞遗传学检测；治疗失败首先可通过PCR检测到，随后是细胞遗传学复发，最后是临床疾病复发。PCR检测最常用于伴有t(14;18)的滤泡性淋巴瘤、伴有t(9;22)的慢性髓性白血病和急性淋巴细胞白血病（ALL）、伴有t(4;11)的ALL以及伴有t(8;21)或t(15;17)的急性髓性白血病（AML）的MRD分析。只要易位与恶性肿瘤高度相关且断点足够集中，PCR扩增就适用于任何其他易位；现在有越来越多这样的特异性分子标志物可用于PCR检测。PCR在检测隐匿性疾病方面仍属实验性研究。然而，由于发现不同疾病实体之间存在显著的预后差异，每种白血病的MRD检测的临床相关性应分别评估。本文综述了可用于检测具有特定染色体易位的白血病细胞的PCR检测方法，并总结了在疾病过程中应用PCR技术监测患者的经验。
