Long noncoding RNAs: emerging regulators of normal and malignant hematopoiesis

Genome-wide analyses have revealed that long noncoding RNAs (lncRNAs) are not only passive transcription products, but also major regulators of genome structure and transcription. In particular, lncRNAs exert profound effects on various biological processes, such as chromatin structure, transcription, RNA stability and translation, and protein degradation and localization, that depend on their localization and interacting partners. Recent studies have revealed that thousands of lncRNAs are aberrantly expressed in various cancer types, and some are associated with malignant transformation. Despite extensive efforts, the diverse functions of lncRNAs and molecular mechanisms in which they act remain elusive. Many hematological disorders and malignancies primarily result from genetic alterations that lead to the dysregulation of gene regulatory networks required for cellular proliferation and differentiation. Consequently, a growing list of lncRNAs has been reported to be involved in the modulation of hematopoietic gene expression networks and hematopoietic stem and progenitor cell (HSPC) function. Dysregulation of some of these lncRNAs has been attributed to the pathogenesis of hematological malignancies. In this review, we summarize current advances and knowledge of lncRNAs in gene regulation, focusing on recent progress on the role of lncRNAs in CTCF/cohesin-mediated 3-dimensional genome organization and how such genome folding signals, in turn, regulate transcription, HSPC function, and transformation. This knowledge will provide mechanistic and translational insights into HSPC biology and myeloid malignancy pathophysiology.