Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, Australia.
Blood Cancer Discov. 2024 Nov 1;5(6):400-416. doi: 10.1158/2643-3230.BCD-24-0103.
Therapy-related myeloid neoplasm (t-MN), characterized by its association with prior exposure to cytotoxic therapy, remains poorly understood and is a major impediment to long-term survival even in the era of novel targeted therapies due to its aggressive nature and treatment resistance. Previously, cytotoxic therapy-induced genomic changes in hematopoietic stem cells were considered sine qua non in pathogenesis; however, recent research demonstrates a complex interaction between acquired and hereditary genetic predispositions, along with a profoundly senescent bone marrow (BM) microenvironment. We review emerging data on t-MN risk factors and explore the intricate interplay among clonal hematopoiesis, genetic predisposition, and the abnormal BM microenvironment. Significance: t-MN represents a poorly understood blood cancer with extremely poor survival and no effective therapies. We provide a comprehensive review of recent preclinical research highlighting complex interaction among emerging therapies, hereditary and acquired genetic factors, and BM microenvironment. Understanding the risk factors associated with t-MN is crucial for clinicians, molecular pathologists, and cancer biologists to anticipate and potentially reduce its incidence in the future. Moreover, better understanding of the molecular pathogenesis of t-MN may enable preemptive screening and even intervention in high-risk patients.
治疗相关髓系肿瘤（t-MN）的特征是与先前接触细胞毒性治疗有关，尽管在新型靶向治疗时代，由于其侵袭性和治疗耐药性，即使长期生存也仍然难以理解，这是一个主要障碍。以前，人们认为细胞毒性治疗诱导造血干细胞的基因组改变是发病机制的必要条件；然而，最近的研究表明，获得性和遗传性遗传易感性以及严重衰老的骨髓（BM）微环境之间存在复杂的相互作用。我们回顾了 t-MN 危险因素的新兴数据，并探讨了克隆性造血、遗传易感性和异常 BM 微环境之间的复杂相互作用。意义：t-MN 代表一种理解甚少的血液癌，其生存率极低，且无有效疗法。我们提供了对新兴治疗方法、遗传和获得性遗传因素以及 BM 微环境之间复杂相互作用的最新临床前研究的全面综述。了解与 t-MN 相关的危险因素对于临床医生、分子病理学家和癌症生物学家预测并可能在未来降低其发病率至关重要。此外，更好地了解 t-MN 的分子发病机制可能能够对高危患者进行预防性筛查甚至干预。
