Cargando…

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

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 bioi...

Descripción completa

Detalles Bibliográficos
Autores principales: Yun, Jae Won, Bae, Yoon Kyung, Cho, So Yeong, Koo, Harim, Kim, Hee-Jin, Nam, Do-Hyun, Kim, Sun-Hee, Chun, Sejong, Joo, Kyeung Min, Park, Woong-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480444/
https://www.ncbi.nlm.nih.gov/pubmed/30959925
http://dx.doi.org/10.3390/ijms20071717
_version_ 1783413569401913344
author Yun, Jae Won
Bae, Yoon Kyung
Cho, So Yeong
Koo, Harim
Kim, Hee-Jin
Nam, Do-Hyun
Kim, Sun-Hee
Chun, Sejong
Joo, Kyeung Min
Park, Woong-Yang
author_facet Yun, Jae Won
Bae, Yoon Kyung
Cho, So Yeong
Koo, Harim
Kim, Hee-Jin
Nam, Do-Hyun
Kim, Sun-Hee
Chun, Sejong
Joo, Kyeung Min
Park, Woong-Yang
author_sort Yun, Jae Won
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6480444
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-64804442019-04-29 Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion Yun, Jae Won Bae, Yoon Kyung Cho, So Yeong Koo, Harim Kim, Hee-Jin Nam, Do-Hyun Kim, Sun-Hee Chun, Sejong Joo, Kyeung Min Park, Woong-Yang Int J Mol Sci Article 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. MDPI 2019-04-06 /pmc/articles/PMC6480444/ /pubmed/30959925 http://dx.doi.org/10.3390/ijms20071717 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yun, Jae Won
Bae, Yoon Kyung
Cho, So Yeong
Koo, Harim
Kim, Hee-Jin
Nam, Do-Hyun
Kim, Sun-Hee
Chun, Sejong
Joo, Kyeung Min
Park, Woong-Yang
Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion
title Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion
title_full Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion
title_fullStr Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion
title_full_unstemmed Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion
title_short Elucidation of Novel Therapeutic Targets for Acute Myeloid Leukemias with RUNX1-RUNX1T1 Fusion
title_sort elucidation of novel therapeutic targets for acute myeloid leukemias with runx1-runx1t1 fusion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480444/
https://www.ncbi.nlm.nih.gov/pubmed/30959925
http://dx.doi.org/10.3390/ijms20071717
work_keys_str_mv AT yunjaewon elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion
AT baeyoonkyung elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion
AT chosoyeong elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion
AT kooharim elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion
AT kimheejin elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion
AT namdohyun elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion
AT kimsunhee elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion
AT chunsejong elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion
AT jookyeungmin elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion
AT parkwoongyang elucidationofnoveltherapeutictargetsforacutemyeloidleukemiaswithrunx1runx1t1fusion