Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, United States; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.
Adv Cancer Res. 2019;141:213-253. doi: 10.1016/bs.acr.2018.12.005. Epub 2019 Jan 21.
Acute myeloid leukemia (AML) derives from the clonal expansion of immature myeloid cells in the bone marrow, and results in the disruption of normal hematopoiesis and subsequent bone marrow failure. The bone marrow microenvironment (BME) and its immune and other supporting cells are regarded to facilitate the survival, differentiation and proliferation of leukemia stem cells (LSCs), which enables AML cells to persist and expand despite treatment. Recent studies have identified epigenetic modifications among AML cells and BME constituents in AML, and have shown that epigenetic therapy can potentially reprogram these alterations. In this review, we summarize the interactions between the BME and LSCs, and discuss changes in how the BME and immune cells interact with AML cells. After describing the epigenetic modifications seen across chromatin, DNA, the BME, and the immune microenvironment, we explore how demethylating agents may reprogram these pathological interactions, and potentially re-sensitize AML cells to treatment.
急性髓系白血病 (AML) 源于骨髓中未成熟髓样细胞的克隆性扩增，导致正常造血功能紊乱和随后的骨髓衰竭。骨髓微环境 (BME) 及其免疫和其他支持细胞被认为有助于白血病干细胞 (LSCs) 的存活、分化和增殖，这使得 AML 细胞能够在治疗后持续存在和扩增。最近的研究已经确定了 AML 中 AML 细胞和 BME 成分之间的表观遗传修饰，并表明表观遗传治疗可能潜在地重新编程这些改变。在这篇综述中，我们总结了 BME 与 LSCs 之间的相互作用，并讨论了 BME 和免疫细胞与 AML 细胞相互作用方式的变化。在描述了染色质、DNA、BME 和免疫微环境中的表观遗传修饰之后，我们探讨了去甲基化剂如何重新编程这些病理性相互作用，并可能使 AML 细胞重新对治疗敏感。
