Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, United States.
Myeloma Division, Department of Medicine, University of Miami Miller School of Medicine, United States.
Leuk Res. 2023 Mar;126:107020. doi: 10.1016/j.leukres.2023.107020. Epub 2023 Jan 20.
Therapy-related myeloid neoplasms (t-MN) account for approximately 10-15% of all myeloid neoplasms and are associated with poor prognosis. Genomic characterization of t-MN to date has been limited in comparison to the considerable sequencing efforts performed for de novo myeloid neoplasms. Until recently, targeted deep sequencing (TDS) or whole exome sequencing (WES) have been the primary technologies utilized and thus limited the ability to explore the landscape of structural variants and mutational signatures. In the past decade, population-level studies have identified clonal hematopoiesis as a risk factor for the development of myeloid neoplasms. However, emerging research on clonal hematopoiesis as a risk factor for developing t-MN is evolving, and much is unknown about the progression of CH to t-MN. In this work, we will review the current knowledge of the genomic landscape of t-MN, discuss background knowledge of clonal hematopoiesis gained from studies of de novo myeloid neoplasms, and examine the recent literature studying the role of therapeutic selection of CH and its evolution under the effects of antineoplastic therapy. Finally, we will discuss the potential implications on current clinical practice and the areas of focus needed for future research into therapy-selected clonal hematopoiesis in myeloid neoplasms.
治疗相关髓系肿瘤(t-MN)约占所有髓系肿瘤的 10-15%,预后不良。与大量针对新发髓系肿瘤进行的测序相比,目前对 t-MN 的基因组特征研究还很有限。直到最近,靶向深度测序(TDS)或全外显子组测序(WES)一直是主要使用的技术,因此限制了探索结构变异和突变特征景观的能力。在过去的十年中,人群水平的研究已经确定克隆性造血是髓系肿瘤发生的一个危险因素。然而,关于克隆性造血作为发展为 t-MN 的危险因素的新兴研究正在不断发展,关于 CH 向 t-MN 进展的许多问题尚不清楚。在这项工作中,我们将回顾 t-MN 的基因组景观的现有知识,讨论从新发髓系肿瘤研究中获得的关于克隆性造血的背景知识,并研究最近研究治疗性选择 CH 及其在抗肿瘤治疗影响下进化作用的文献。最后,我们将讨论对当前临床实践的潜在影响以及未来研究髓系肿瘤中治疗选择的克隆性造血需要关注的领域。