Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 467, Issue 4, Pages 742-747Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.10.071
Keywords
Acute myeloid leukemia; HOXB2; HOXB3; FLT3; STAT5; Colony formation
Categories
Funding
- Kungliga Fysiografiska Sallskapet i Lund [20141112]
- Ollie and Elof Ericssons Stiftelse [20140908]
- Ake-Wiberg Stiftelse [134061257]
- Lars Hiertas Minne Stiftelse [FO2014-0302]
- Stiftelsen Olle Engkvist Byggmastare [20130128]
- Harald Jeanssons Stiftelse
- Harald och Greta Jeanssons Stiftelse [20141114]
- Swedish Childhood Cancer Foundation [PR2014-0059]
- Crafoord foundation [20150760]
- Stiftelsen Clas Groschinskys Minnesfond [M15 96]
- Gunnar Nilssons Cancer Foundation [CAN 201404]
- Swedish Cancer Society [CAN 2012/781]
- Swedish Research Council [CAN 2013-3728]
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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 AML 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 colony formation and increased apoptosis. Expression of HOXB2 or HOXB3 resulted in a significant decrease in FLT3-ITD-induced AKT, ERR, p38 and STAT5 phosphorylation. Our data suggest that HOXB2 and HOXB3 act as tumor suppressors in FLT3-ITD driven AML. (C) 2015 Elsevier Inc. All rights reserved.
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