The role of HOXB2 and HOXB3 in acute myeloid leukemia.
Research output: Contribution to journal › Article
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.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2015|
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Related research output
FLT3 and KIT in acute myeloid leukemia. Translational studies on oncogenic signaling from receptor tyrosine kinases. Translational studies on oncogenic signaling from receptor tyrosine kinasesOSCAR LINDBLAD, 2016, Lund: Lund University, Faculty of Medicine. 56 p.
Research output: Thesis › Doctoral Thesis (compilation)