急性骨髓性白血病（AML）是一种异质性疾病，其遗传、表观遗传和转录起源主要表现为体细胞和生殖细胞的异常。AML的发病率随着年龄的增长而上升，但也可能在儿童时期发生。小儿AML（pAML）占所有小儿白血病的15-20％，与成人AML有很大的区别。下一代测序技术使研究社区能够“描绘”基因组和表观基因组景观，以确定与病理相关的突变和其他预后生物标志物在pAML中的存在。尽管目前的治疗已经改善了pAML的预后，但化疗抗性、复发和难治疾病仍然是主要的挑战。特别是，pAML的复发通常是由抵抗治疗的白血病干细胞引起的。明显的患者异质性很可能是相同治疗对一些患者成功，但对其他患者最多只有部分有效的主要原因。越来越多的证据表明，患者特异性克隆组成对细胞过程，如基因调控和代谢，产生重大影响。尽管我们对pAML中的代谢仍处于萌芽状态，但对这些过程及其（表观）调节的更深入了解可能为新的治疗选择铺平道路。在本综述中，我们总结了有关遗传和表观遗传（失）调节在pAML中的功能的当前知识，包括观察到的代谢特征。具体而言，我们描述了（表观）遗传机制如何在造血过程中影响染色质状态，导致代谢剖面发生改变，并专注于在pAML的精准和联合治疗中针对表观遗传异常的潜在价值。我们还讨论了使用已经在临床实践中的替代性表观药物治疗方法的可能性，单独作为辅助治疗和/或与其他药物联合使用。版权所有©2023。由Elsevier Ltd.发表。

Acute myeloid leukemia (AML) is a heterogeneous disease with a genetic, epigenetic, and transcriptional etiology mainly presenting somatic and germline abnormalities. AML incidence rises with age but can also occur during childhood. Pediatric AML (pAML) accounts for 15-20% of all pediatric leukemias and differs considerably from adult AML. Next-generation sequencing technologies have enabled the research community to "paint" the genomic and epigenomic landscape in order to identify pathology-associated mutations and other prognostic biomarkers in pAML. Although current treatments have improved the prognosis for pAML, chemoresistance, recurrence, and refractory disease remain major challenges. In particular, pAML relapse is commonly caused by leukemia stem cells that resist therapy. Marked patient-to-patient heterogeneity is likely the primary reason why the same treatment is successful for some patients but, at best, only partially effective for others. Accumulating evidence indicates that patient-specific clonal composition impinges significantly on cellular processes, such as gene regulation and metabolism. Although our understanding of metabolism in pAML is still in its infancy, greater insights into these processes and their (epigenetic) modulation may pave the way toward novel treatment options. In this review, we summarize current knowledge on the function of genetic and epigenetic (mis)regulation in pAML, including metabolic features observed in the disease. Specifically, we describe how (epi)genetic machinery can affect chromatin status during hematopoiesis, leading to an altered metabolic profile, and focus on the potential value of targeting epigenetic abnormalities in precision and combination therapy for pAML. We also discuss the possibility of using alternative epidrug-based therapeutic approaches that are already in clinical practice, either alone as adjuvant treatments and/or in combination with other drugs.Copyright © 2023. Published by Elsevier Ltd.