表观遗传学
髓系白血病
疾病
白血病
造血
免疫学
生物
表观遗传疗法
髓样
癌症研究
医学
干细胞
生物信息学
DNA甲基化
内科学
基因
遗传学
基因表达
作者
Xin Zhao,Huan‐Qiu Liu,Lina Wang,Le Yang,Xiaoliang Liu
标识
DOI:10.1016/j.semcancer.2020.11.010
摘要
Acute myeloid leukemia (AML) is the most frequently diagnosed acute leukemia, and its incidence increases with age. Although the etiology of AML remains unknown, exposure to genotoxic agents or some prior hematologic disorders could lead to the development of this condition. The pathogenesis of AML involves the development of malignant transformation of hematopoietic stem cells that undergo successive genomic alterations, ultimately giving rise to a full-blown disease. From the disease biology perspective, AML is considered to be extremely complex with significant genetic, epigenetic, and phenotypic variations. Molecular and cytogenetic alterations in AML include mutations in those subsets of genes that are involved in normal cell proliferation, maturation and survival, thus posing significant challenge to targeting these pathways without attendant toxicity. In addition, multiple malignant cells co-exist in the majority of AML patients. Individual subclones are characterized by unique genetic and epigenetic abnormalities, which contribute to the differences in their response to treatment. As a result, despite a dramatic progress in our understanding of the pathobiology of AML, not much has changed in therapeutic approaches to treat AML in the past four decades. Dose and regimen modifications with improved supportive care have contributed to improved outcomes by reducing toxicity-related side effects. Several drug candidates are currently being developed, including targeted small-molecule inhibitors, cytotoxic chemotherapies, monoclonal antibodies and epigenetic drugs. This review summarizes the current state of affairs in the pathobiological and therapeutic aspects of AML.
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