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The role of HOXB2 and HOXB3 in acute myeloid leukemia.

Lindblad, Oscar LU ; Chougule, Rohit A. LU ; Moharram, Sausan A. LU ; Kabir, Nuzhat N; Sun, Jianmin LU ; Kazi, Julhash U. LU and Rönnstrand, Lars LU (2015) In Biochemical and Biophysical Research Communications 467(4). p.742-747
Abstract
Acute myeloid leukemia (AML) is a heterogeneous aggressive disease and the most common form of adult leukemia. Mutations in the type III receptor tyrosine kinase FLT3 are found in more than 30% of patients. Drugs against FLT3 have been developed for the treatment of AML, but they lack specificity, show poor response and lead to the development of a resistant phenotype upon treatment. Therefore, a deeper understanding of FLT3 signaling will facilitate identification of additional pharmacological targets in FLT3-driven AML. In this report, we identify HOXB2 and HOXB3 as novel regulators of oncogenic FLT3-ITD-driven AML. We show that HOXB2 and HOXB3 expression is upregulated in a group of AML patients carrying FLT3-ITD. Overexpression of... (More)
Acute myeloid leukemia (AML) is a heterogeneous aggressive disease and the most common form of adult leukemia. Mutations in the type III receptor tyrosine kinase FLT3 are found in more than 30% of patients. Drugs against FLT3 have been developed for the treatment of AML, but they lack specificity, show poor response and lead to the development of a resistant phenotype upon treatment. Therefore, a deeper understanding of FLT3 signaling will facilitate identification of additional pharmacological targets in FLT3-driven AML. In this report, we identify HOXB2 and HOXB3 as novel regulators of oncogenic FLT3-ITD-driven AML. We show that HOXB2 and HOXB3 expression is upregulated in a group of AML patients carrying FLT3-ITD. Overexpression of HOXB2 or HOXB3 in mouse pro-B cells resulted in decreased FLT3-ITD-dependent cell proliferation as well as decreased colony formation and increased apoptosis. Expression of HOXB2 or HOXB3 resulted in a significant decrease in FLT3-ITD-induced AKT, ERK, p38 and STAT5 phosphorylation. Our data suggest that HOXB2 and HOXB3 act as a tumor suppressors in FLT3-ITD driven AML. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
467
issue
4
pages
742 - 747
publisher
Elsevier
external identifiers
  • pmid:26482852
  • wos:000365145300022
  • scopus:84946605856
ISSN
1090-2104
DOI
10.1016/j.bbrc.2015.10.071
language
English
LU publication?
yes
id
21bd247d-17a5-4cb7-854f-ca516ac48882 (old id 8148844)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26482852?dopt=Abstract
date added to LUP
2015-11-03 18:31:56
date last changed
2017-07-09 03:13:01
@article{21bd247d-17a5-4cb7-854f-ca516ac48882,
  abstract     = {Acute myeloid leukemia (AML) is a heterogeneous aggressive disease and the most common form of adult leukemia. Mutations in the type III receptor tyrosine kinase FLT3 are found in more than 30% of patients. Drugs against FLT3 have been developed for the treatment of AML, but they lack specificity, show poor response and lead to the development of a resistant phenotype upon treatment. Therefore, a deeper understanding of FLT3 signaling will facilitate identification of additional pharmacological targets in FLT3-driven AML. In this report, we identify HOXB2 and HOXB3 as novel regulators of oncogenic FLT3-ITD-driven AML. We show that HOXB2 and HOXB3 expression is upregulated in a group of AML patients carrying FLT3-ITD. Overexpression of HOXB2 or HOXB3 in mouse pro-B cells resulted in decreased FLT3-ITD-dependent cell proliferation as well as decreased colony formation and increased apoptosis. Expression of HOXB2 or HOXB3 resulted in a significant decrease in FLT3-ITD-induced AKT, ERK, p38 and STAT5 phosphorylation. Our data suggest that HOXB2 and HOXB3 act as a tumor suppressors in FLT3-ITD driven AML.},
  author       = {Lindblad, Oscar and Chougule, Rohit A. and Moharram, Sausan A. and Kabir, Nuzhat N and Sun, Jianmin and Kazi, Julhash U. and Rönnstrand, Lars},
  issn         = {1090-2104},
  language     = {eng},
  number       = {4},
  pages        = {742--747},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {The role of HOXB2 and HOXB3 in acute myeloid leukemia.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2015.10.071},
  volume       = {467},
  year         = {2015},
}