Belitsky Gennady, Fetisov Timur, Kirsanov Kirill, Lesovaya Ekaterina, Vlasova Olga, Yakubovskaya Marianna
Department of Chemical Carcinogenesis, Blokhin National Medical Research Center of Oncology, Ministry of Health of Russian Federation Moscow 115478, Russia.
Faculty of Basic Therapy, Peoples' Friendship University of Russia Moscow 117198, Russia.
Am J Blood Res. 2020 Dec 15;10(6):416-433. eCollection 2020.
Secondary tumors, including therapy-related acute myeloid leukemia (t-AML), represent one of the most undesirable side effects of chemotherapy, which arise several years after primary cancer treatment. This review aims to analyze the current data on molecular pathogenesis of t-AML revealing potential criteria for predicting predisposition to the disease. Another objective is to analyze the information on promising approaches for t-AML prevention.
We analyzed studies regarding t-AML and possible approaches for cancer prevention of drug-induced tumors. Publications in the databases, such as SciVerse Scopus (948), PubMed (1837) and Web of Science (935) were used. Among 92 the most important publications cited in the review, 79 were published during the last decade.
The review provides the information concerning t-AML pathogenesis, molecular markers of primary cancer patients with high risk of t-AML. The role of the bone marrow niche in clonal hematopoiesis and t-AML pathogenesis is discussed. Current approaches for t-AML prevention both at the stage of therapy and at the latent period are described. Inhibition effects of polyphenols on cell proliferation and on the appearance of hemopoetic clones of indeterminate potential are proposed for t-AML prevention.
The problem of the t-AML, a cancer induced by genotoxic chemotherapeutic drugs, is considered from the point of view of the fundamental mechanisms of chemical carcinogenesis, highlighting initiation and promotion stages. It enables to reveal the possible markers for the group of patients with high risk for t-AML and to demonstrate perspectives for the use of plant polyphenols for t-AML prevention.
继发性肿瘤,包括治疗相关的急性髓系白血病(t-AML),是化疗最不良的副作用之一,在原发性癌症治疗数年之后出现。本综述旨在分析目前关于t-AML分子发病机制的数据,揭示预测该疾病易感性的潜在标准。另一个目标是分析有关t-AML预防的有前景方法的信息。
我们分析了关于t-AML以及药物诱导肿瘤癌症预防可能方法的研究。使用了诸如SciVerse Scopus(948篇)、PubMed(1837篇)和Web of Science(935篇)等数据库中的出版物。在该综述引用的92篇最重要的出版物中,79篇是在过去十年发表的。
该综述提供了有关t-AML发病机制、t-AML高风险原发性癌症患者分子标志物的信息。讨论了骨髓微环境在克隆性造血和t-AML发病机制中的作用。描述了在治疗阶段和潜伏期预防t-AML的当前方法。提出多酚对细胞增殖和不确定潜能造血克隆出现的抑制作用可用于预防t-AML。
从化学致癌基本机制的角度考虑了由基因毒性化疗药物诱导的癌症t-AML问题,突出了启动和促进阶段。这有助于揭示t-AML高风险患者群体的可能标志物,并展示使用植物多酚预防t-AML的前景。