Super-Enhancers Dysregulations in Hematological Malignancies

Abstract

Hematological malignancies affecting either the lymphoid or the myeloid lineages involve epigenetic mutations or dysregulation in the majority of cases. These epigenetic abnormalities can affect regulatory elements in the genome and, particularly, enhancers. Recently, large regulatory elements known as super-enhancers, initially identified for their critical roles in cell-type specific expression regulation of genes controlling cell identity, have been shown to also be involved in tumorigenesis in many cancer types and hematological malignancies via the regulation of numerous oncogenes, including MYC. In this review, we highlight the existing links between super-enhancers and hematological malignancies, with a particular focus on acute myeloid leukemia, a clonal hematopoietic neoplasm with dismal outcomes, resulting in an uncontrolled proliferation of myeloblasts, abnormally blocked during differentiation and accumulating within the patient’s bone marrow. We report recent works, performed during the last few years, treating this subject and consider the possibility of targeting oncogenic regulatory elements, as well as the effectiveness and limitations reported so far for such strategies.

Keywords

• enhancers
• super-enhancers
• regulatory elements
• acute myeloid leukemia
• hematological malignancies
• enhancer hijacking