Colmenares Rafael, Álvarez Noemí, Barrio Santiago, Martínez-López Joaquín, Ayala Rosa
Hematology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Imas12, 28041 Madrid, Spain.
Hematological Malignancies Clinical Research Unit, CNIO, 28029 Madrid, Spain.
Cancers (Basel). 2022 Mar 3;14(5):1310. doi: 10.3390/cancers14051310.
The study of cell-free DNA (cfDNA) and other peripheral blood components (known as "liquid biopsies") is promising, and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing a greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsies. Most of the studies about this topic have focused on B-cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for the diagnosis and minimal residual monitoring of B-cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of the early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real time. However, there are limitations, such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess the minimal residual disease, or the lack of standardization of the method, and clinical studies, to confirm its prognostic impact. This review focuses on the clinical applications of cfDNA on the minimal residual disease in hematological malignancies.
对游离DNA（cfDNA）和其他外周血成分（即“液体活检”）的研究前景广阔，尤其在实体瘤研究中备受关注。然而，其在血液系统恶性肿瘤的诊断、预后评估及治疗反应监测方面的应用价值日益凸显；未来，它有望取代诸如骨髓活检等侵入性技术。关于这一主题的大多数研究都聚焦于B细胞淋巴系统恶性肿瘤；其中一些研究表明，利用下一代测序（NGS）等技术，cfDNA可作为诊断B细胞淋巴瘤及进行微小残留病监测的新方法。在骨髓增生异常综合征、多发性骨髓瘤或慢性淋巴细胞白血病中，液体活检或许能为影响不同病灶的肿瘤克隆提供有价值的基因组特征（空间异质性）。在急性白血病中，它有助于监测早期治疗反应及预测治疗失败。在慢性淋巴细胞白血病中，对cfDNA的评估可实时明确克隆演变及耐药情况。然而，也存在一些局限性，比如难以获取足够的循环肿瘤DNA以实现评估微小残留病的高灵敏度，或者该方法及临床研究缺乏标准化，从而无法证实其预后影响。本综述聚焦于cfDNA在血液系统恶性肿瘤微小残留病方面的临床应用。
