Enhancing Targeted Therapy for Myeloproliferative Neoplasms.

摘要

Myeloproliferative neoplasms (MPNs) are blood cancers that affect almost 300,000 people in the United States. MPN drugs (JAK inhibitors) do not effectively induce remission. 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, which is prevented by the addition of mevalonate. Statin treatment also inhibited the colony formation of primary cells from MPN patients, but not from healthy individuals. Statin treatment alone or in combination with a JAK2 inhibitor did not affect disease formation in an MPN mouse model, suggesting statin effects on MPN cells may be restricted to in vitro experiments, or that the effects of statins on MPN cells in vivo requires doses of drug that have not been tested or are unattainable. While evidence that cholesterol plays a role in MPNs continues to mount, our work suggests additional research is required to determine if statins should be considered in a potential therapeutic strategy for MPNs.