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

Autor: Yoon Kyung Bae, Hee Jin Kim, Woong-Yang Park, Sun-Hee Kim, Harim Koo, Jae Won Yun, Do Hyun Nam, Sejong Chun, Kyeung Min Joo, So Yeong Cho
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Oncogene Proteins
Fusion
oncogenes
lcsh:Chemistry
Fusion gene
RUNX1 Translocation Partner 1 Protein
0302 clinical medicine
hemic and lymphatic diseases
Receptors
Platelet-Derived Growth Factor
lcsh:QH301-705.5
transcription factor
Spectroscopy
biology
General Medicine
Middle Aged
Computer Science Applications
Leukemia
Myeloid
Acute
Fibroblast growth factor receptor
030220 oncology & carcinogenesis
Core Binding Factor Alpha 2 Subunit
embryonic structures
Female
Signal transduction
Platelet-derived growth factor receptor
Adult
acute myeloid leukemia
Article
Catalysis
Cell Line
Inorganic Chemistry
03 medical and health sciences
Growth factor receptor
Humans
Physical and Theoretical Chemistry
neoplasms
Molecular Biology
Gene
Transcription factor
RUNX1-RUNX1T1
Organic Chemistry
Computational Biology
Fusion protein
Receptors
Vascular Endothelial Growth Factor
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Cancer research
Transcription Factors
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 20, Iss 7, p 1717 (2019)
Volume 20
Issue 7
ISSN: 1422-0067
DOI: 10.3390/ijms20071717
Popis: 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.
Databáze: OpenAIRE
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