Therapy-Related Myeloid Neoplasms: Complex Interactions among Cytotoxic Therapies, Genetic Factors, and Aberrant Microenvironment.

IF 11.5 Q1 HEMATOLOGY Blood Cancer Discovery Pub Date : 2024-11-01 DOI:10.1158/2643-3230.BCD-24-0103
Deepak Singhal, Monika M Kutyna, Christopher N Hahn, Mithun Vinod Shah, Devendra K Hiwase
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Abstract

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.

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与治疗相关的骨髓性肿瘤:细胞毒性疗法、遗传因素和异常微环境之间的复杂互动。
治疗相关性髓样肿瘤(t-MN)的特点是与之前接受细胞毒性治疗有关,但人们对它的了解仍然很少,即使在新型靶向疗法时代,由于其侵袭性和耐药性,它仍是长期生存的主要障碍。以前,细胞毒治疗诱导的造血干细胞基因组变化被认为是发病的必要条件;然而,最近的研究表明,获得性和遗传性遗传倾向与深度衰老的骨髓(BM)微环境之间存在复杂的相互作用。我们回顾了有关 t-MN 风险因素的新数据,并探讨了克隆造血、遗传易感性和异常骨髓微环境之间错综复杂的相互作用。意义:t-MN 是一种鲜为人知的血癌,生存率极低,且没有有效的治疗方法。我们对最近的临床前研究进行了全面回顾,强调了新兴疗法、遗传和获得性遗传因素以及生物膜微环境之间复杂的相互作用。了解与 t-MN 相关的风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有助于对高危患者进行先期筛查甚至干预。
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来源期刊
CiteScore
12.70
自引率
1.80%
发文量
139
期刊介绍: The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes. The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence. Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.
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