Leukemia, although most likely starts as a monoclonal genetic/epigenetic anomaly, is a polyclonal disease at manifestation. This polyclonal nature results from ongoing evolutionary changes in the genome/epigenome of leukemia cells to promote their survival and proliferation advantages. We discuss here how genetic and/or epigenetic aberrations alter intracellular microenvironment in individual leukemia clones and how extracellular microenvironment selects the best fitted clones. This dynamic polyclonal composition of leukemia makes designing an effective therapy a challenging task especially because individual leukemia clones often display substantial differences in response to treatment. Here, we discuss novel therapeutic approach employing single cell multiomics to identify and eradicate all individual clones in a patient.

白血病虽然最有可能以单克隆遗传/表观遗传异常开始，但在表现时是一种多克隆疾病。这种多克隆性质是白血病细胞基因组/表观基因组持续进化变化的结果，以促进其存活和增殖优势。我们在这里讨论遗传和/或表观遗传畸变如何改变单个白血病克隆的细胞内微环境，以及细胞外微环境如何选择最合适的克隆。白血病的这种动态多克隆组成使得设计有效的疗法成为一项具有挑战性的任务，特别是因为单个白血病克隆对治疗的反应通常表现出很大差异。在这里，我们讨论了采用单细胞多组学来识别和根除患者体内所有个体克隆的新型治疗方法。