MicroRNA-155 expression and function in AML: An evolving paradigm

Abstract

Acute myeloid leukemia (AML) arises when immature myeloid blast cells acquire multiple, recurrent genetic and epigenetic changes that result in dysregulated proliferation. Acute leukemia is the most common form of pediatric cancer, with AML accounting for ~20% of all leukemias in children. The genomic aberrations that drive AML inhibit myeloid differentiation and activate signal transduction pathways that drive proliferation. MicroRNAs, a class of small (~22 nucleotide) noncoding RNAs that posttranscriptionally suppress the expression of specifically targeted transcripts, are also frequently dysregulated in AML, which may prove useful for the purposes of disease classification, prognosis, and future therapeutic approaches. MicroRNA expression profiles are associated with patient prognosis and responses to standard chemotherapy, including predicting therapy resistance in AML. miR-155 is the primary focus of this review because it has been repeatedly associated with poorer survival across multiple cohorts of adult and pediatric AML. We discuss some novel features of miR-155 expression in AML, in particular how the levels of expression can critically influence function. Understanding the role of microRNAs in AML and the ways in which microRNA expression influences AML biology is one means to develop novel and more targeted therapies.

Role of microRNA dysregulation in childhood acute leukemias: diagnostics, monitoring and therapeutics: A comprehensive review

“…A consistent and strong association of miR-155 overexpression with poor prognosis in pediatric AML was also confirmed[ 110 - 112 ]. An interesting relationship between the level of expression of miR-155, its biological function and prognosis in AML was noted by Narayan et al[ 105 , 111 ]. Researchers conducted experiments on cells obtained from patients diagnosed with AML and on a murine model, where they found that between 10- and 50-fold overexpression of miR-155 (plays the role of oncogene) is associated with poorer OS and increased tumor burden.…”

“…MiR-155 is evolutionarily conserved, and as an inhibitor of lineage differentiation, it is one of the most critical regulators of posttranscriptional gene expression in B cells[ 101 , 102 ]. It has also been confirmed to be associated with pathogenesis, aggressiveness and progression in CLL[ 103 , 104 ]; poor survival in adult and pediatric AML[ 105 ]; and poor clinical prognosis in Hodgkin's lymphomas[ 106 ] and B-cell-type Diffuse large B-cell lymphoma[ 107 , 108 ]. El-Khazragy et al[ 109 ] tried to connect the upregulation of miRNA-155a and miRNA-181a expression to ALL outcome.…”

“…The consequence of differentiated miR-155 expression is downregulation of the expression of target genes regulated by intermediate ( CEBPB , SPI1 , and TLE2 ) or high ( MYB and KIT ) miR-155 expression levels. Narayan et al[ 105 , 111 ] first described a novel dose-dependent function of miR-155 in the progression of AML and pointed out that it can have important therapeutic implications.…”

Prognostic and Clinicopathological Significance of MiR-155 in Hematologic Malignancies: A Systematic Review and Meta-analysis

“…5. Altered expression of miR-155 has been reported in several hematologic malignancies 2, 6-10, including diffuse large B-cell lymphoma (DLBCL), Hodgkin's lymphoma (HL), follicular lymphoma (FL), acute myeloid leukemia (AML), acute and chronic lymphoblastic leukemia (ALL, CLL), and myelodysplastic syndrome (MDS). Upregulated miR-155 expression was further associated with tumor progression and poor prognosis in several reports.…”

MiR-663, a MicroRNA Linked with Inflammation and Cancer That Is under the Influence of Resveratrol

“…MicroRNAs are small (19–23-nt in length) non-coding regulatory RNAs that regulate the stability and/or translation of their target transcripts. MicroRNAs have been progressively implicated in all aspects of cell biology and homeostasis and established as key players in a number of pathologies, including, but not limited to, inflammatory, metabolic and cardiovascular diseases, neuropathologies, and cancers [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”