Publication Date:
2011-11-18
Description:
Abstract 798FN2 Background: Ruxolitinib (INC424), a potent and selective oral JAK1 and JAK2 inhibitor, has demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms, role functioning, and quality of life in 2 phase 3 studies in patients with myelofibrosis. Panobinostat, a potent oral pan-deacetylase inhibitor (pan-DACi) that increases acetylation of proteins involved in multiple oncogenic pathways, has shown encouraging clinical activity in phase 1/2 trials of myelofibrosis. Here, we investigate the combination of ruxolitinib and panobinostat in mouse models of JAK2V617F-driven disease. Methods: Scid-beige female mice were randomized to treatment groups on the basis of baseline bioluminescence 4 days after injection of Ba/F3 EpoR JAK2V617F-luciferase cells. Mice were treated with vehicle control, panobinostat (4, 8, or 12 mg/kg intraperitoneal 3 times a week) alone or in combination with ruxolitinib (60 mg/kg orally twice daily), or ruxolitinib alone (n=7 each). Whole-body bioluminescence imaging was conducted on days 7 and 11. Spleens were weighed and extracts were obtained to determine levels of phosphorylated STAT5 (p-STAT5) and lysine acetylation. Results: Imaging on day 11 showed luminescence reductions (P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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