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Review
. 2016 Dec 10;17(12):2080.
doi: 10.3390/ijms17122080.

Therapeutic Resistance in Acute Myeloid Leukemia: The Role of Non-Coding RNAs

Armin Zebisch  1 , Stefan Hatzl  2 , Martin Pichler  3 , Albert Wölfler  4 , Heinz Sill  5
Affiliations
Review

Therapeutic Resistance in Acute Myeloid Leukemia: The Role of Non-Coding RNAs

Armin Zebisch et al. Int J Mol Sci. .

Abstract

Acute myeloid leukemia (AML) is caused by malignant transformation of hematopoietic stem or progenitor cells and displays the most frequent acute leukemia in adults. Although some patients can be cured with high dose chemotherapy and allogeneic hematopoietic stem cell transplantation, the majority still succumbs to chemoresistant disease. Micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs) are non-coding RNA fragments and act as key players in the regulation of both physiologic and pathologic gene expression profiles. Aberrant expression of various non-coding RNAs proved to be of seminal importance in the pathogenesis of AML, as well in the development of resistance to chemotherapy. In this review, we discuss the role of miRNAs and lncRNAs with respect to sensitivity and resistance to treatment regimens currently used in AML and provide an outlook on potential therapeutic targets emerging thereof.

Keywords: acute myeloid leukemia; chemoresistance; long non-coding RNA; micro-RNA; risk stratification.

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Conflict of interest statement

Conflicts of InterestArmin Zebisch reports receiving honoraria from Celgene. Heinz Sill reports receiving research support and honoraria from Celgene. Albert Wölfler reports receiving research support from Celgene and honoraria from Celgene and Janssen-Cilag.

Figures

Figure 1
Figure 1
Example of a miRNA network influencing therapeutic sensitivity in acute myeloid leukemia (AML) high-intensity treatment. N-terminal mutations in CEBPA enable translation of a truncated CEBPA-p30 isoform, which in turn induces miR-181a [58]. As a consequence, BCL-2—a direct miR-181a target—is downregulated, which in turn increases the sensitivity to both cytarabine and daunorubicin [49,50,58]. Interestingly, expression of CEBPA-p30 is induced by lenalidomide as well [58].
Figure 2
Figure 2
Example of a miRNA network influencing therapeutic sensitivity in AML low-intensity treatment. Gain of function mutations of KIT occur in AML and have been shown to decrease miR-29b expression levels via upregulation of the MYC oncogene. As a result, downregulation of the miR-29b target DNMT3A is prevented. This is of relevance for decitabine treatment, which has been shown to inhibit DNMT3A activity and which has proven to be more efficient, when DNMT3A levels are low [79,82,84].
See this image and copyright information in PMC

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