Deep-sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia
Deep-sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia
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DOI：
10.1182/blood-2012-07-444042
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发表时间：
2012-12-20
期刊：
影响因子：
20.3
通讯作者：
Campana, Dario
中科院分区：
文献类型：
--
作者：
Faham, Malek;Zheng, Jianbiao;Campana, Dario
治疗期间微小残留病（MRD）的持续存在是急性淋巴细胞白血病（ALL）最强的不良预后因素。我们开发了一种高通量测序方法，可以普遍扩增抗原受体基因片段并在诊断时识别所有克隆基因重排（即白血病特异性序列），从而可以在治疗期间监测疾病进展和克隆进化。在本研究中，该测定在掺入实验中从超过 100 万个白细胞中特异性检测到了 1 个白血病细胞。我们使用来自 106 名 ALL 患者的诊断和随访样本，将此方法与金标准 MRD 测定多参数流式细胞术和等位基因特异性寡核苷酸聚合酶链反应 (ASO-PCR) 进行比较。测序在流式细胞术显示为阳性的所有 28 个样本中检测到 MRD，在 ASO-PCR 显示为阳性的 36 个样本中的 35 个中检测到 MRD，并分别在流式细胞术和 ASO-PCR 为阴性的 10 个和 3 个附加样本中检测到 MRD。我们的结论是，这种新方法可以以极高的灵敏度和精确度监测 ALL 和其他淋巴恶性肿瘤的治疗反应。 Total XV 研究的 www.clinicaltrials.gov 标识符号为 NCT00137111。 （血。2012；120（26）：5173-5180）
The persistence of minimal residual disease (MRD) during therapy is the strongest adverse prognostic factor in acute lymphoblastic leukemia (ALL). We developed a high-throughput sequencing method that universally amplifies antigen-receptor gene segments and identifies all clonal gene rearrangements (ie, leukemia-specific sequences) at diagnosis, allowing monitoring of disease progression and clonal evolution during therapy. In the present study, the assay specifically detected 1 leukemic cell among greater than 1 million leukocytes in spike-in experiments. We compared this method with the gold-standard MRD assays multiparameter flow cytometry and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) using diagnostic and follow-up samples from 106 patients with ALL. Sequencing detected MRD in all 28 samples shown to be positive by flow cytometry and in 35 of the 36 shown to be positive by ASO-PCR and revealed MRD in 10 and 3 additional samples that were negative by flow cytometry and ASO-PCR, respectively. We conclude that this new method allows monitoring of treatment response in ALL and other lymphoid malignancies with great sensitivity and precision. The www.clinicaltrials.gov identifier number for the Total XV study is NCT00137111. (Blood. 2012; 120(26): 5173-5180)