Prime time for the use of statins in MPNs - from comorbidity drugs to disease-modifying partners

Sep 22, 2026

Upload by Adam

Review article tracing a 20-year evolution of the statin-in-MPN concept in Philadelphia chromosome–negative myeloproliferative neoplasms. It frames MPNs as a human inflammation model where chronic inflammation drives clonal expansion, premature atherosclerosis, fibrogenesis, and higher risk of second cancers and comorbidities. Statins are discussed for pleiotropic anti-inflammatory, antiproliferative, proapoptotic, antiangiogenic, antifibrotic, and antithrombotic actions, including evidence from epidemiology and emerging clinical data combining statins with interferon alpha and other agents to improve outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Prime time for the use of statins in MPNs: from comorbidity drugs to disease-modifying partners

Historical background

Statins: beyond cholesterol-lowering

Inflammation

REVIEW ARTICLE Prime time for the use of statins in MPNs: from comorbidity drugs to disease-modifying partners Hans C. Hasselbalch Department of Hematology, Zealand University Hospital, Roskilde, Denmark For over 2 decades, the mevalonate pathway has been in focus as an interesting therapeutic target in Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs). Initially explored for its potential in cytoreductive and antithrombotic therapy, the role of statins in MPNs is now experiencing a compelling renaissance. This renewed interest is fueled by the recognition of MPNs as “a human inflammation model,” driven by chronic inflammation that fuels clonal expansion, premature atherosclerosis, fibrogenesis, and an increased risk of second cancers and comorbidities. Statins possess a wide spectrum of pleiotropic effects beyond lipid lowering, including anti-inflammatory, antiproliferative, proapoptotic, antiangiogenic, and antifibrotic properties. They dampen the activation of leukocytes, platelets, and endothelial cells. Recent epidemiological studies from Denmark demonstrate that statins protect against the development of MPNs in the general population. Furthermore, emerging clinical data suggest that statins enhance the efficacy of interferon alpha (IFN-α), the only known therapy capable of directly targeting the malignant stem cell and inducing minimal residual disease in a subset of patients. This review traces the 20-year journey of the statin-in-MPN concept, from its mechanistic rationale to the present, in which a confluence of evidence from comorbid disease prevention and oncoimmunology is supportive of their upfront use. I posit that we are at a watershed moment, at which statins should be integrated into the upfront treatment of MPNs and in combination therapy strategies, particularly with IFN-α, and potentially with ruxolitinib and metformin, to extinguish the chronic inflammatory drive and fundamentally alter the natural history of these neoplasms. Historical background Approximately 20 years ago, I had the privilege of guest-editing a theme issue in Current Drug Targets dedicated to “Highlights on Important Signaling Pathways in Hematological Malignancies”. In that issue, we contributed a paper focusing on the relevance of the mevalonate pathway (MVP) in polycythemia vera (PV) and related neoplasms, 1 building on a hypothesis described 1 year earlier in which we proposed statins as both antithrombotic and cytoreductive agents in patients with myeloproliferative neoplasms (MPNs) .2 Despite a compelling preclinical rationale, translational progress stalled. A planned randomized controlled trial in patients with newly diagnosed MPN was abandoned because enrollment was expected to be prohibitive: a large proportion of patients aged > 60 years were already receiving statins for cardiovascular indications. Submitted 7 January 2026; accepted 15 February 2026; prepublished online on Blood Advances First Edition 26 February 2026. [https://doi.org/10.1182/blood](https://doi.org/10.1182/blood)advances.2026019625. © 2026 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. 26 MAY 2026 • VOLUME 10, NUMBER 10 3587 The hypothesis was revitalized with my Blood Perspective in 2012, which for the first time positioned chronic inflammation as a central driver of premature atherosclerosis, clonal evolution, and second cancers in MPNs.3 Within this framework, the pleiotropic antiinflammatory properties of statins emerged as a potentially powerful therapeutic modality. Now, decades later, a wealth of epidemiologic and clinical data has accumulated, supporting statin use in MPNs and in cancer biology more broadly.4-15 Accordingly, rationales for statin therapy have repeatedly been highlighted in reviews a

FAQs

Why are statins considered promising in MPNs beyond lipid lowering?

Statins have pleiotropic effects including anti-inflammatory, antiproliferative, proapoptotic, antiangiogenic, antifibrotic, and antithrombotic properties. These actions can dampen activation of leukocytes, platelets, and endothelial cells.

What role does chronic inflammation play in MPNs according to the review?

MPNs are described as a human inflammation model in which chronic inflammation drives clonal expansion, premature atherosclerosis, fibrogenesis, and increased risk of second cancers and comorbidities.

How might statins be integrated into MPN treatment strategies?

The review argues for integrating statins into upfront treatment and combination therapy, particularly with interferon alpha, and potentially with ruxolitinib and metformin. The goal is to extinguish inflammatory drive and alter the natural history of these neoplasms.

Sep 22, 2026

Upload by Adam