What Lies Beneath: A Look at MPN as Inflammatory Diseases
By Marina Sampanes Peed
Cytokine storms brew beneath the surface, wreaking havoc on our system and causing intolerable pain. The referrals to specialists yield no improvement…
I was eager to hear Dr. Hans Hasselbalch’s ‘early bird presentation’ on research and treatment of MPN with a focus on their inflammation damage to the body. As one who struggled with significant and painful inflammation issues when my Polycythemia Vera got “angry,” I was desperate for science to catch up with my condition.
Dr. Hasselbalch is a clinical researcher at the University of Copenhagen’s Roskilde Hospital in Denmark. He shared perspectives on the “Early Interferon Concept: Combination therapy with Ruxolitinib and Interferon.” His presentation referenced several studies and I’ve included the main points of interest to patients in this article.
Chronic Inflammation Triggers More Disease
Chronic inflammation contributes to oxidative stress and genomic instability that leads to clonal evolution in the human body. The inflammation causes additional driver mutations occur, with additional subclone mutations occurring in later stages. When chronic inflammation is very active, ET and PV are moved to an accelerated phase which causes Myelofibrosis and eventually Acute Leukemia.
Chronic Inflammation Changes the Microenvironment
Dr. Hasselbalch and others discussed the microenvironment that affects the MPN mutations and contribute to the inflammation issues. When cytokines and other inflammatory agents are activated, they trigger endothelial dysfunction and systemic inflammation. (Endothelial cells line the blood vessels). Inflammation affects the circulatory system and causes swelling and redness in extremities (he called them ‘microcirculatory disturbances’). You may have experienced red toes and fingers from time to time. Inflammation often contributes to spleen expansion.
Inflammation can trigger Thrombosis
A link between chronic inflammation and thrombosis in MPNs has been documented and reported in Italy. Inflammation and thrombosis in ET and PV: a different role of C-reactive protein and Pentraxin 3. When platelets and leukocytes interact in an inflamed environment, thromboembolic events can occur – in micro vessels and significant vessels such as the portal vein.
MPNs and Autoimmune Diseases
New research is finding common features with MPN inflammation and autoimmune responses. A cytokine profiling study in myelofibrosis patients identified ten types of cytokines that were elevated in patients. Some of these cytokines are prominent in auto-immune diseases.
Benefits of Early Intervention with Interferon-alpha and JAK Inhibitors
The best way to quell the inflammation is early intervention – before chronic phase and accelerated phase. Stop the fuel supply (cell activation) with Interferon-alpha; and fight the inflammation with JAK1-2 inhibitor and statins.
Treated with Interferon-alpha soon after diagnosis, MPN patients achieve: normal blood counts; cytogenetic remission; molecular remission; normal bone marrow; and minimal residual disease. These results are documented in studies conducted in Denmark.
For patients living with painful “side effects” caused by internal inflammation, this research is encouraging. We can’t make progress if no one is working on the problem. Hopefully, Dr. Hasselbalch’s research will continue and stimulate further investigation.
© 2015, MPNforum, LLC. All rights reserved under Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License
Leave a Reply