Next Article in Journal
Development and Palatability Assessment of Norvir® (Ritonavir) 100 mg Powder for Pediatric Population
Previous Article in Journal
Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response
Open AccessArticle

Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion

1
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea
2
Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
3
Single Cell Network Research Center, Sungkyunkwan University of Medicine, Suwon 16419, Korea
4
Department of Anatomy and Cell biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea
5
Departments of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
6
Department of Laboratory Medicine, Chonnam National University Medical School & Hospital, Gwangju 61469, Korea
7
Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea
8
Departments of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(7), 1717; https://doi.org/10.3390/ijms20071717
Received: 5 March 2019 / Revised: 2 April 2019 / Accepted: 4 April 2019 / Published: 6 April 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
The RUNX1-RUNX1T1 fusion is a frequent chromosomal alteration in acute myeloid leukemias (AMLs). Although RUNX1-RUNX1T1 fusion protein has pivotal roles in the development of AMLs with the fusion, RUNX1-RUNX1T1, fusion protein is difficult to target, as it lacks kinase activities. Here, we used bioinformatic tools to elucidate targetable signaling pathways in AMLs with RUNX1-RUNX1T1 fusion. After analysis of 93 AML cases from The Cancer Genome Atlas (TCGA) database, we found expression of 293 genes that correlated to the expression of the RUNX1-RUNX1T1 fusion gene. Based on these 293 genes, the cyclooxygenase (COX), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) pathways were predicted to be specifically activated in AMLs with RUNX1-RUNX1T1 fusion. Moreover, the in vitro proliferation of AML cells with RUNX1-RUNX1T1 fusion decreased significantly more than that of AML cells without the fusion, when the pathways were inhibited pharmacologically. The results indicate that novel targetable signaling pathways could be identified by the analysis of the gene expression features of AMLs with non-targetable genetic alterations. The elucidation of specific molecular targets for AMLs that have a specific genetic alteration would promote personalized treatment of AMLs and improve clinical outcomes. View Full-Text
Keywords: acute myeloid leukemia; RUNX1-RUNX1T1; oncogenes; transcription factor acute myeloid leukemia; RUNX1-RUNX1T1; oncogenes; transcription factor
Show Figures

Figure 1

MDPI and ACS Style

Yun, J.W.; Bae, Y.K.; Cho, S.Y.; Koo, H.; Kim, H.-J.; Nam, D.-H.; Kim, S.-H.; Chun, S.; Joo, K.M.; Park, W.-Y. Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion. Int. J. Mol. Sci. 2019, 20, 1717.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop