Circular RNAs in Hematopoiesis with a Focus on Acute Myeloid Leukemia and Myelodysplastic Syndrome

Abstract

Circular RNAs (circRNAs) constitute a recently recognized group of noncoding transcripts that function as posttranscriptional regulators of gene expression at a new level. Recent developments in experimental methods together with rapidly evolving bioinformatics approaches have accelerated the exploration of circRNAs. The differentiation of hematopoietic stem cells into a broad spectrum of specialized blood lineages is a tightly regulated process that depends on a multitude of factors, including circRNAs. However, despite the growing number of circRNAs described to date, the roles of the majority of them in hematopoiesis remain unknown. Given their stability and disease-specific expression, circRNAs have been acknowledged as novel promising biomarkers and therapeutic targets. In this paper, the biogenesis, characteristics, and roles of circRNAs are reviewed with an emphasis on their currently recognized or presumed involvement in hematopoiesis, especially in acute myeloid leukemia and myelodysplastic syndrome.

The Role of Non-Coding RNAs in Myelodysplastic Neoplasms

“…The hypothesis of circRNAs interfering with MDS pathophysiology was supported by the observation that exogenous inhibition of the spliceosome components, commonly affected by MDS mutated genes, can cause an imbalance between circular and linear RNA concentrations within affected cells towards overexpression of the circular molecules [94,95]. Wedge et al recently reported that specific cancer-associated circRNAs, such as circZNF609 and circCSNK1G3, are upregulated in MDS patients with U2AF1 mutations compared to unmutated controls [96].…”

Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia

“…One of the earliest studies to describe circRNAs in hematopoiesis was published in 1998 by Caldas et al (47) in which they introduced splicing of the MLL gene, a frequently rearranged gene in a variety of hematological malignancies, which is involved in a complex process that results in the formation of abnormal transcripts with different genomic orientation, scrambled transcripts, and circRNAs in both normal and leukemic cells. Research on hematopoiesis-related circRNAs has grown rapidly since NGS emerged, and the catalog of these circRNAs has dramatically expanded (48). For example, it is known that circ-BACH1 (exons 2-4) is mainly expressed in hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), whereas circ-FNDC3B (exon 5-6) is broadly expressed in natural killer (NK) cells, circ-ELK4 (exon 4-3), circ-SLFN12L (exon 2-3) and circ-MYBL1 (exon 12-7) are preferentially expressed in T cells and NK cells, circ-AKT3 and circ-CCDC91 were found to be expressed across lymphoid cells (49).…”

Zebrafish: a convenient tool for myelopoiesis research

“…Noncoding RNAs are emerging regulatory factors for myelopoiesis, including lncRNAs (Qiu et al 2021 ) and circRNAs (Dostalova Merkerova et al 2020 ). In addition, many microRNAs have been found to be regulators or effectors of myelopoietic transcription factors (Kim et al 2019 ).…”