Advanced

BEX1 acts as a tumor suppressor in acute myeloid leukemia.

Lindblad, Oscar LU ; Li, Tianfeng; Su, Xianwei; Sun, Jianmin LU ; Kabir, Nuzhat N; Levander, Fredrik LU ; Zhao, Hui; Lu, Gang; Rönnstrand, Lars LU and Kazi, Julhash U. LU (2015) In Oncotarget 6(25). p.21395-21405
Abstract
Acute myeloid leukemia (AML) is a heterogeneous disease of the myeloid lineage. About 35% of AML patients carry an oncogenic FLT3 mutant making FLT3 an attractive target for treatment of AML. Major problems in the development of FLT3 inhibitors include lack of specificity, poor response and development of a resistant phenotype upon treatment. Further understanding of FLT3 signaling and discovery of novel regulators will therefore help to determine additional pharmacological targets in FLT3-driven AML. In this report, we identified BEX1 as a novel regulator of oncogenic FLT3-ITD-driven AML. We showed that BEX1 expression was down-regulated in a group of AML patients carrying FLT3-ITD. Loss of BEX1 expression resulted in poor overall... (More)
Acute myeloid leukemia (AML) is a heterogeneous disease of the myeloid lineage. About 35% of AML patients carry an oncogenic FLT3 mutant making FLT3 an attractive target for treatment of AML. Major problems in the development of FLT3 inhibitors include lack of specificity, poor response and development of a resistant phenotype upon treatment. Further understanding of FLT3 signaling and discovery of novel regulators will therefore help to determine additional pharmacological targets in FLT3-driven AML. In this report, we identified BEX1 as a novel regulator of oncogenic FLT3-ITD-driven AML. We showed that BEX1 expression was down-regulated in a group of AML patients carrying FLT3-ITD. Loss of BEX1 expression resulted in poor overall survival (hazard ratio, HR = 2.242, p = 0.0011). Overexpression of BEX1 in mouse pro-B and myeloid cells resulted in decreased FLT3-ITD-dependent cell proliferation, colony and tumor formation, and in increased apoptosis in vitro and in vivo. BEX1 localized to the cytosolic compartment of cells and significantly decreased FLT3-ITD-induced AKT phosphorylation without affecting ERK1/2 or STAT5 phosphorylation. Our data suggest that the loss of BEX1 expression in FLT3-ITD driven AML potentiates oncogenic signaling and leads to decreased overall survival of the patients. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Oncotarget
volume
6
issue
25
pages
21395 - 21405
publisher
Impact Journals, LLC
external identifiers
  • pmid:26046670
  • wos:000360969200054
  • scopus:84940766860
ISSN
1949-2553
language
English
LU publication?
yes
id
361b25ca-3d30-41b0-89a3-7411e708b756 (old id 7488134)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26046670?dopt=Abstract
date added to LUP
2015-07-06 16:33:19
date last changed
2017-11-05 04:13:35
@article{361b25ca-3d30-41b0-89a3-7411e708b756,
  abstract     = {Acute myeloid leukemia (AML) is a heterogeneous disease of the myeloid lineage. About 35% of AML patients carry an oncogenic FLT3 mutant making FLT3 an attractive target for treatment of AML. Major problems in the development of FLT3 inhibitors include lack of specificity, poor response and development of a resistant phenotype upon treatment. Further understanding of FLT3 signaling and discovery of novel regulators will therefore help to determine additional pharmacological targets in FLT3-driven AML. In this report, we identified BEX1 as a novel regulator of oncogenic FLT3-ITD-driven AML. We showed that BEX1 expression was down-regulated in a group of AML patients carrying FLT3-ITD. Loss of BEX1 expression resulted in poor overall survival (hazard ratio, HR = 2.242, p = 0.0011). Overexpression of BEX1 in mouse pro-B and myeloid cells resulted in decreased FLT3-ITD-dependent cell proliferation, colony and tumor formation, and in increased apoptosis in vitro and in vivo. BEX1 localized to the cytosolic compartment of cells and significantly decreased FLT3-ITD-induced AKT phosphorylation without affecting ERK1/2 or STAT5 phosphorylation. Our data suggest that the loss of BEX1 expression in FLT3-ITD driven AML potentiates oncogenic signaling and leads to decreased overall survival of the patients.},
  author       = {Lindblad, Oscar and Li, Tianfeng and Su, Xianwei and Sun, Jianmin and Kabir, Nuzhat N and Levander, Fredrik and Zhao, Hui and Lu, Gang and Rönnstrand, Lars and Kazi, Julhash U.},
  issn         = {1949-2553},
  language     = {eng},
  number       = {25},
  pages        = {21395--21405},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {BEX1 acts as a tumor suppressor in acute myeloid leukemia.},
  volume       = {6},
  year         = {2015},
}