Enhancing Targeted Therapy for Myeloproliferative Neoplasms
Abstract
Myeloproliferative neoplasms (MPNs) are blood cancers that affect almost 300,000 people in the United States. While recent drugs (JAK inhibitors) have been developed to treat MPNs these drugs do not effectively induce remission in MPN patients. Thus there is continued need to develop effective therapies for these blood cancers. The purpose of this work is to determine the effect of statins alone and in combination with JAK inhibition on MPN cells driven by the JAK2-V617F oncogene. We have determined that statins have growth inhibitory effects on MPN cells and induce cell death by apoptosis. Addition of mevalonate prevents statin-induced growth inhibition demonstrating the effect is through the intended inhibition of the mevalonate pathway. Statin treatment also inhibited the colony formation of primary cells from MPN patients. Similar statin treatment did not inhibit colony formation of primary cells from healthy individuals. Using an MPN mouse model, statin treatment alone did not affect disease formation. These studies have set up our studies for year two where we will combine statin and JAK inhibitor treatment to study the effects of combination therapy on MPN cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA600492
Entities
People
- Gary W. Reuther
Organizations
- H. Lee Moffitt Cancer Center & Research Institute