A guide to epigenetics in leukaemia stem cells.
A guide to epigenetics in leukaemia stem cells.
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DOI：
10.1002/1878-0261.13544
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发表时间：
2023-12
影响因子：
6.6
通讯作者：
Huntly, Brian J. P.
中科院分区：
文献类型：
--
作者：
Agrawal-Singh, Shuchi;Bagri, Jaana;Sakakini, Nathalie;Huntly, Brian J. P.
关键词：
白血病干细胞(LSCs)是血液系统恶性肿瘤生长的关键种子细胞，驱动克隆性扩增，使疾病发生、复发和耐药成为可能。具体地说，它们表现出固有的表型和表观遗传可塑性，导致复杂的异质性疾病。在这篇综述中，我们讨论了放松表观遗传过程的关键原则，这些过程塑造了这种疾病的演变。我们考虑了定义和量化克隆异质性的方法，结合了最近评估髓系肿瘤(MN)单细胞分辨率下突变、转录和表观遗传学的信息。我们强调整合表观遗传和遗传信息的重要性，以更好地了解患者之间和患者内部的异质性，并讨论这种理解如何进一步告知MN的进化和进展轨迹以及随后的临床反应。在这一主题下，我们还讨论了通过对患者样本的纵向分析来确定耐药机制的努力。最后，我们强调我们可能如何针对这些异常的表观遗传过程，以获得更好的治疗结果，并有可能根除LSCs。在白血病干细胞(LSCs)中，异常的表观遗传机制汇聚并建立肿瘤内的异质性，支持白血病的生长。这些异常机制直接位于表观遗传突变的下游，或间接与代谢和细胞外源信号有关。除了启动和维持LSC状态外，这些异常机制还提供了潜在的靶向漏洞，以帮助根除LSC和治疗白血病。
Leukaemia stem cells (LSCs) are the critical seed for the growth of haematological malignancies, driving the clonal expansion that enables disease initiation, relapse and often resistance. Specifically, they display inherent phenotypic and epigenetic plasticity resulting in complex heterogenic diseases. In this review, we discuss the key principles of deregulation of epigenetic processes that shape this disease evolution. We consider measures to define and quantify clonal heterogeneity, combining information from recent studies assessing mutational, transcriptional and epigenetic landscapes at single cell resolution in myeloid neoplasms (MN). We highlight the importance of integrating epigenetic and genetic information to better understand inter‐ and intra‐patient heterogeneity and discuss how this understanding further informs evolution and progression trajectories and subsequent clinical response in MN. Under this topic, we also discuss efforts to identify mechanisms of resistance, by longitudinal analyses of patient samples. Finally, we highlight how we might target these aberrant epigenetic processes for better therapeutic outcomes and to potentially eradicate LSCs. In leukaemic stem cells (LSCs), aberrant epigenetic mechanisms converge and establish intratumoral heterogeneity, supporting leukaemic growth. These aberrant mechanisms lie directly downstream of epigenetic mutations or indirectly relate to metabolic and cell‐extrinsic signalling. Besides initiating and maintaining the LSC state, these aberrant mechanisms also provide potentially targetable vulnerabilities to help eradicate LSC and cure leukaemias.
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影响因子：
50.3
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Jordan CT
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23.9
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Jordan, Craig T.
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Levine RL
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82.9
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通讯作者：
Mason CE
影响因子：
45.3
作者：
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通讯作者：
Kwong, YL