INSERM U944, CNRS UMR7212, Institut de Recherche Saint Louis, Université de Paris, 75010 Paris, France.
Cells. 2022 Jan 7;11(2):196. doi: 10.3390/cells11020196.
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.
影响淋巴或髓系的血液系统恶性肿瘤在大多数情况下涉及表观遗传突变或失调。这些表观遗传异常可以影响基因组中的调节元件,特别是增强子。最近,被称为超级增强子的大型调节元件,最初因其在控制细胞身份的基因的细胞类型特异性表达调控中的关键作用而被识别,已被证明也参与许多癌症类型和血液系统恶性肿瘤的肿瘤发生,通过调节许多癌基因,包括 MYC。在这篇综述中,我们强调了超级增强子与血液系统恶性肿瘤之间的现有联系,特别关注急性髓系白血病,这是一种预后不良的克隆性造血肿瘤,导致成髓细胞的不受控制增殖,在分化过程中异常受阻并在患者骨髓中积累。我们报告了过去几年中针对这一主题的最新研究工作,并考虑了针对致癌调节元件的可能性,以及迄今为止针对这些策略的有效性和局限性。