Enhancers control dynamic changes in gene expression and orchestrate the tightly controlled transcriptional circuitries that direct and coordinate cell growth, proliferation, survival, lineage commitment, and differentiation during lymphoid development. Enhancer hijacking and neoenhancer formation at oncogene loci, as well as aberrant activation of oncogene-associated enhancers, can induce constitutive activation of self-perpetuating oncogenic transcriptional circuitries, and contribute to the malignant transformation of immature lymphoid progenitors in acute lymphoblastic leukemia (ALL). In this review, we present recent discoveries of the role of enhancer dynamics in mouse and human lymphoid development, and discuss how genetic and epigenetic alterations of enhancer function can promote leukemogenesis, and potential strategies for targeting the enhancer machinery in the treatment of ALL.

增强子控制基因表达的动态变化，并协调严格控制的转录电路，指导和协调淋巴发育过程中的细胞生长、增殖、存活、谱系定型和分化。癌基因位点的增强子劫持和新增强子的形成，以及癌基因相关增强子的异常激活，可以诱导自我延续的致癌转录电路的组成性激活，并导致急性淋巴细胞白血病 (ALL) 中未成熟淋巴祖细胞的恶性转化。在这篇综述中，我们介绍了增强子动力学在小鼠和人类淋巴发育中的作用的最新发现，并讨论了增强子功能的遗传和表观遗传改变如何促进白血病发生，