急性髓性白血病(AML)是成人中最常见的白血病,死亡率高。当前的诊断标准和治疗策略的选择通常基于基因突变和细胞遗传学异常。化疗,靶向治疗,造血干细胞移植(HSCT)是AML的主要治疗策略。AML的临床管理中的两个困境与其不良预后有关。一个是诊断时不准确的风险分层,导致错误的治疗选择。另一种是对化疗和/或靶向治疗的频繁抗性。基因组特征一直是AML研究的焦点。然而,DNA水平畸变并不总是预测基因和蛋白质的表达水平,后者与疾病表型更密切相关.随着高通量测序和质谱技术的发展,研究下游效应物,包括RNA,蛋白质,和代谢物成为可能。转录组学可以揭示基因表达和调控网络,蛋白质组学可以发现与疾病密切相关的蛋白质表达和信号通路,代谢组学可以反映疾病进展过程中代谢物的精确变化。此外,单细胞水平的组学分析能够研究AML微环境的细胞成分和层次结构。来自不同组学层次的丰富数据通过识别预后相关的生物标志物,能够更好地对AML进行风险分层。并在确定药物靶标方面具有前瞻性应用,因此,有可能找到解决这两个困境的方法。在这次审查中,我们总结了使用组学方法的现有AML研究,无论是单独还是组合,涵盖疾病诊断的研究领域,风险分层,预后预测,化疗,以及靶向治疗。最后,我们讨论了多组学在AML精准医学中的应用方向和挑战。我们的评论可能会激发组学研究人员和临床医生从不同的角度研究AML。
Acute myeloid leukemia (
AML) is the most frequent leukemia in adults with a high mortality rate. Current diagnostic criteria and selections of therapeutic strategies are generally based on gene mutations and cytogenetic abnormalities. Chemotherapy, targeted therapies, and hematopoietic stem cell transplantation (HSCT) are the major therapeutic strategies for
AML. Two dilemmas in the clinical management of
AML are related to its poor prognosis. One is the inaccurate risk stratification at diagnosis, leading to incorrect treatment selections. The other is the frequent resistance to chemotherapy and/or targeted therapies. Genomic features have been the focus of
AML studies. However, the DNA-level aberrations do not always predict the expression levels of genes and proteins and the latter is more closely linked to disease phenotypes. With the development of high-throughput sequencing and mass spectrometry technologies, studying downstream effectors including RNA, proteins, and metabolites becomes possible. Transcriptomics can reveal gene expression and regulatory networks, proteomics can discover protein expression and signaling pathways intimately associated with the disease, and metabolomics can reflect precise changes in metabolites during disease progression. Moreover, omics profiling at the single-cell level enables studying cellular components and hierarchies of the AML microenvironment. The abundance of data from different omics layers enables the better risk stratification of AML by identifying prognosis-related biomarkers, and has the prospective application in identifying drug targets, therefore potentially discovering solutions to the two dilemmas. In this review, we summarize the existing
AML studies using omics methods, both separately and combined, covering research fields of disease diagnosis, risk stratification, prognosis prediction, chemotherapy, as well as targeted therapy. Finally, we discuss the directions and challenges in the application of multi-omics in precision medicine of AML. Our review may inspire both omics researchers and clinical physicians to study AML from a different angle.