英国EAST ANGLIA大学 骨髓微环境是产生白血病的最重要因素

The bone marrow microenvironment – Home of the leukemic blasts

急性髓系白血病(Acute Myeloid leukemia, AML)是一种在遗传、生物学和临床方面均表现出异质性的疾病，其特征是骨髓(BM)中异常髓系祖细胞的生长增多。

急性髓系白血病( AML)其特征是骨髓(BM)中异常髓系祖细胞的生长增多。

体外AML表现出高度的自发性凋亡。此外，在骨髓微环境中存在的最小残留癌细胞可使患者缓解的病人复发。综上所述，这些观察说明了骨髓微环境在维持急性髓系白血病中的重要性。

急性髓系白血病( AML)其特征是骨髓(BM)中异常髓系祖细胞的生长增多

虽然阐述小规模基因突变和大规模的染色体易位导致AML的发展及其预后治疗,，已取得显著进展，对骨髓的微环境知之甚少，骨髓微环境在这种疾病的发病机制中发挥重要作用。

当我们展望未来的治疗, 考虑骨髓微环境对急性髓系白血病的重要性，白血病干细胞更容易遗传不稳定，因此发展抵抗常规治疗，使良性细胞的骨髓功能成为有吸引力的治疗靶点。

在这篇综述中，我们讨论了骨髓的显微解剖，并概述了支持骨髓微环境在创造有利于AML细胞存活和增殖条件中的作用的证据。

急性髓系白血病( AML)其特征是骨髓(BM)中异常髓系祖细胞的生长增多

最后，我们检验从骨髓微环境中分离AML的治疗潜力。

The bone marrow microenvironment – Home of the leukemic blasts

Author links open overlay panelManar SShafataBrunoGnaneswaranbKristian MBowlesacStuart ARushwortha

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https://doi.org/10.1016/j.blre.2017.03.004Get rights and content

Abstract

Acute Myeloid Leukaemia (AML) is a genetically, biologically and clinically heterogeneous set of diseases, which are characterised by an increased growth of abnormal myeloid progenitor cells within the bone marrow (BM). Ex-vivo AML exhibits a high level of spontaneous apoptosis. Furthermore, relapse for patients achieving remission occurs from minimal residual disease harboured within the BM microenvironment. Taken together, these observations illustrate the importance of the BM microenvironment in sustaining AML. While significant progress has been made elaborating the small-scale genetic mutations and larger-scale chromosomal translocations that contribute to the development of AML and its prognosis in response to treatment, less is understood about the complex microenvironment of the BM, which is known to be a key player in the pathogenesis of the disease. As we look towards future therapies, the consideration that the BM microenvironment is uniquely important as a niche for AML - coupled with the idea that leukaemic blasts are more likely to be genetically unstable and therefore evolve resistance to conventional chemotherapies - make the functions of the non-malignant cells of the BM attractive targets for therapy. In this review, we discuss the microanatomy of the BM and provide an overview of the evidence supporting the role of the BM microenvironment in creating conditions conducive to the survival and proliferation of AML blasts. Ultimately, we examine the therapeutic potential of uncoupling AML from the BM microenvironment.

https://www.sciencedirect.com/science/article/pii/S0268960X1630073X