Deregulation of enhancer structure, function, and dynamics in acute lymphoblastic leukemia

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.