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Biochem Biophys Res Commun. 2015 Nov 27;467(4):742-7. doi: 10.1016/j.bbrc.2015.10.071. Epub 2015 Oct 22.

The role of HOXB2 and HOXB3 in acute myeloid leukemia.

Author information

1
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden; Department of Hematology and Vascular Disorders, Skåne University Hospital, Lund, Sweden.
2
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden.
3
Laboratory of Computational Biochemistry, KN Biomedical Research Institute, Barisal, Bangladesh.
4
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden; Laboratory of Computational Biochemistry, KN Biomedical Research Institute, Barisal, Bangladesh.
5
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden. Electronic address: lars.ronnstrand@med.lu.se.

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 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, ERK, p38 and STAT5 phosphorylation. Our data suggest that HOXB2 and HOXB3 act as tumor suppressors in FLT3-ITD driven AML.

KEYWORDS:

Acute myeloid leukemia; Colony formation; FLT3; HOXB2; HOXB3; STAT5

PMID:
26482852
DOI:
10.1016/j.bbrc.2015.10.071
[Indexed for MEDLINE]

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