The role of HOXB2 and HOXB3 in acute myeloid leukemia.

Summary, in English

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: Oscar Lindblad; Rohit A. Chougule; Sausan A. Moharram; Nuzhat N Kabir; Jianmin Sun; Julhash U. Kazi; Lars Rönnstrand
• Department/s: Division of Translational Cancer Research; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2015
• Language: English
• Pages: 742-747
• Publication/Series: Biochemical and Biophysical Research Communications
• Volume: 467
• Issue: 4
• Full text: - 1009 kB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26482852?dopt=Abstract; http://dx.doi.org/10.1016/j.bbrc.2015.10.071
• Document type: Journal article
• Publisher: Elsevier
• Topic: Hematology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1090-2104