Sperotto Alessandra, Bochicchio Maria Teresa, Simonetti Giorgia, Buccisano Francesco, Peccatori Jacopo, Piemontese Simona, Calistri Elisabetta, Ciotti Giulia, Pierdomenico Elisabetta, De Marchi Roberta, Ciceri Fabio, Gottardi Michele
Onco Hematology, Department of Oncology, Veneto Institute of Oncology, IOV-IRCCS, 31033 Padua, Italy.
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 46046 Meldola, Italy.
Biomedicines. 2023 Jan 26;11(2):359. doi: 10.3390/biomedicines11020359.
It has now been ascertained that acute myeloid leukemias-as in most type of cancers-are mixtures of various subclones, evolving by acquiring additional somatic mutations over the course of the disease. The complexity of leukemia clone architecture and the phenotypic and/or genotypic drifts that can occur during treatment explain why more than 50% of patients-in hematological remission-could relapse. Moreover, the complexity and heterogeneity of clone architecture represent a hindrance for monitoring measurable residual disease, as not all minimal residual disease monitoring methods are able to detect genetic mutations arising during treatment. Unlike with chemotherapy, which imparts a relatively short duration of selective pressure on acute myeloid leukemia clonal architecture, the immunological effect related to allogeneic hematopoietic stem cell transplant is prolonged over time and must be overcome for relapse to occur. This means that not all molecular abnormalities detected after transplant always imply inevitable relapse. Therefore, transplant represents a critical setting where a measurable residual disease-based strategy, performed during post-transplant follow-up by highly sensitive methods such as next-generation sequencing, could optimize and improve treatment outcome. The purpose of our review is to provide an overview of the role of next-generation sequencing in monitoring both measurable residual disease and clonal evolution in acute myeloid leukemia patients during the entire course of the disease, with special focus on the transplant phase.
现已确定，与大多数癌症类型一样，急性髓系白血病是各种亚克隆的混合物，在疾病过程中通过获得额外的体细胞突变而演变。白血病克隆结构的复杂性以及治疗期间可能发生的表型和/或基因型漂移解释了为什么超过50%处于血液学缓解期的患者会复发。此外，克隆结构的复杂性和异质性对监测可测量的残留疾病构成了障碍，因为并非所有最小残留疾病监测方法都能够检测治疗期间出现的基因突变。与化疗不同，化疗对急性髓系白血病克隆结构施加的选择性压力持续时间相对较短，而异基因造血干细胞移植的免疫效应会随着时间延长，并且复发必须克服这种效应。这意味着移植后检测到的并非所有分子异常都必然意味着不可避免的复发。因此，移植是一个关键阶段，在此阶段通过下一代测序等高灵敏度方法在移植后随访期间实施基于可测量残留疾病的策略，可以优化和改善治疗结果。我们综述的目的是概述下一代测序在监测急性髓系白血病患者整个疾病过程中的可测量残留疾病和克隆演变方面的作用，特别关注移植阶段。
