General AML

The role and therapeutic implications of miRNAs in AML

Jared A. Wallace and Ryan M. O’Connell from the University of Utah, Salt Lake City, USA, have written an insightful review on the role of Micro RNAs (miRNAs) and the therapeutic implications of these biomarkers in patients with Acute Myeloid Leukemia (AML). The review was published ahead of print in Blood on 27th July 2017.

miRNAs are small non-coding RNAs (approximately 20–24 nucleotides) that play a crucial role in post-transcriptional gene regulation through repression of target messenger RNAs. Different miRNA profiles have been reported in different subtypes of AML and they can impact leukemogenesis and disease progression via collaboration with oncogenes or tumor suppressors. Additionally, dysregulated miRNAs have been reported to be associated with outcomes in AML patients. Thus, the authors discussed the biology of miRNAs and how it could be used strategically to design therapies for AML.

Dysregulated miRNA expression in AML

In AML, aberrant expression of miRNAs can occur via different mechanisms including epigenetic alterations and targeting by dysregulated transcription factors or oncogenic fusion proteins. The authors noted that aberrant miRNA levels that are observed in AML are largely driven by altered transcription of miRNA transcripts thus suggesting that targeting key transcription factors or epigenetic regulators could be used to restore normal miRNA function in AML.

miRNAs as biomarkers

Specific subtypes and mutant drivers of AML are associated with distinctive miRNA expression profiles thus indicating that they could be used in the classification of AML at diagnosis. Additionally, it has been reported that miRNA expression at diagnosis adds significant prognostic information in AML patients. Furthermore, it has also been proposed that miRNA serum expression should be screened following standard chemotherapy. miRNA serum expression levels in AML patients are different in healthy controls, thus suggesting that miRNA could be used as a marker for monitoring Minimal Residual Disease (MRD) in AML patients.

miRNA directed therapies

Some studies have demonstrated the efficacy of miRNA directed therapy. For example, targeted delivery of miR-29b via transferrin-conjugated lipid nanoparticles led to a decreased leukemic growth and prolonged survival in preclinical models. Additionally, pevonedistat (reduces NF-κB signaling) has been shown to decrease the levels of oncogenic miR-155 thereby decreasing leukemic phenotypes in FLT3-ITD AML preclinical models. However, the authors highlighted that the use of miRNA directed therapy has not advanced into clinical practice.

Emerging concepts for miRNA directed therapies

Several studies have reported that miRNAs including miR-146a can disrupt the normal function of NF-κB signaling, which could lead to the development of AML. The authors noted that the role of miRNAs in NF-κB signaling suggests that targeting these innate immune pathways may have clinical efficacy. Other ways in which miRNA could be explored were discussed including the varying levels of miRNA, the context dependent role of miRNA, as well as the source and non-canonical targeting of miRNAs.


miRNAs play a critical role in AML pathogenesis. Furthermore, “specific miRNA expression profiles can help classify subtype, determine prognosis and predict response to treatment in AML”. The authors however noted that the use of “miRNAs as biomarkers is not yet routine practice”.

The authors concluded by highlighting that there are still unanswered questions on the functions of miRNAs in AML, which they hope that if answered would provide improved understanding of the mechanisms which could be used to “exploit miRNAs therapeutically” and improve disease outcomes for patients with AML.


Acute myeloid leukemia (AML) is a deadly hematologic malignancy characterized by the uncontrolled growth of immature myeloid cells. Over the past several decades we have learned a tremendous amount regarding the genetic aberrations that govern disease development in AML. Among these are genes that encode non-coding RNAs, including the microRNA (miRNA) family. miRNAs are evolutionary conserved small non-coding RNAs that display important physiological effects through their post-transcriptional regulation of messenger RNA (mRNA) targets. Over the past decade, studies have identified miRNAs as playing a role in nearly all aspects of AML disease development, including cellular proliferation, survival, and differentiation. These observations have led to the study of miRNAs as biomarkers of disease, and efforts to therapeutically manipulate miRNAs to improve disease outcome in AML are ongoing. While much has been learned regarding the importance of miRNAs in AML disease initiation and progression, there are many unanswered questions and emerging facets of miRNA biology that add complexity to their roles in AML. Moving forward, answers to these questions will provide a greater level of understanding of miRNA biology and critical insights into the many translational applications for these small regulatory RNAs in AML.

  1. Wallace J.A. & O’Connell R.M. MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts. Blood. 2017 Jul 21. DOI: 10.1182/blood-2016-10-697698. [Epub ahead of print].