« Clinical evidence that JAK2 inhibition by ruxolitinib in MF neither reliably reduces malignant clonal burden nor eliminates cytokine elevations, suggests targeting cytokine mediated signaling as a therapeutic strategy, which is being pursued in new clinical trials »
« The clearly prominent role of inflammation in the pathophysiology of MPNs has led to the hope that inflammatory signaling, either between or within cells, could be manipulated to lead to improved options for treatment. »
« A one-size-fits-all treatment is not likely to be effective for all stages of MPNs. Rather, there remains the hope that some selective treatment targeting the malignant clone might be useful at multiple stages, in conjunction with stage-specific treatments to be used in combination therapy – JAK inhibitors, anti-inflammatory agents, pro-apoptotic agents, and other signaling inhibitors – wherein might lie some hope for patients to be cured pharmacologically rather than exclusively by transplant. »
Well that's interesting. I think, from posts I read, that ruxolitinib helps to reduce spleen size. And is used in combination with Hyrea or Interferon. It's good to know there has been trials on it and it doesn't reduce the inflammation levels. So we won't depend on it in vain to do that. It's reassuring to know these trials are on going. And thank you for your research and posting.
« The deep interconnection between chronic inflammation and cancer was effectively encapsulated in Harold Dvorak’s seminal definition of tumors, in the late 1980s, as “wounds that do not heal” [4]. More recently, the concept of “tumor-associated immune dysregulation” has been introduced to describe tumor cell capability to hijack the wound healing program and generate a permissive microenvironment enabling immunosurveillance escape and tumor growth ».
« The concept of “onco-inflammation” has been recently proposed to depict this complex cross-talk between cancer cells and their inflammatory microenvironment ».
« Hasselbalch has recently portrayed MPNs as a “human inflammation model for cancer development” in which a chronic inflammatory state is at the core of a self-perpetrating vicious cycle leading to complications that punctuate MPN natural history »
« Overall, these initial studies paved the way for the more recent concept of MPNs as a biological continuum with escalation of inflammation as the disease progresses »
« Therefore, based on this literature review, the concept of ET as the form of MPN characterized by a lower inflammatory burden and milder prognosis (lower MF- and AML-transformation rates as compared to PV and survival similar to matched control population should probably be carefully reconsidered. Indeed, the MPN Landmark Survey clearly demonstrated that ET patients experience a plethora of symptoms that is similar to the other MPN subtype (MF, 78%; PV, 88%; ET, 81%), with fatigue being the most frequently reported [82], and this can be attributable to cytokine deregulation »
« Therefore, a therapeutic strategy based on the combination of different immunomodulatory/anti-inflammatory agents (Interferons, IMIDs, steroids, HDACi) appears rational, potentially providing a more effective disease control »
« Given this scenario, it is therefore clear that somatic mutations in the neoplastic clone are not the only players in determining the inflammatory burden in MPNs, and other elements, such as inherited genetic predisposition factors, influencing cytokine production, cytokine-signaling activation levels (i.e., NF-kB), and disease phenotype »
« In addition to acquired somatic mutations, inherited host genetic variants are emerging as important players in modulating individual pro-inflammatory backgrounds. Therefore, we can envision a scenario in which the acquisition of somatic mutation(s) may result in different MPN phenotypes according to host genetic variations affecting the individual inflammatory state. Hence, the “bad soil” which enables the growth and expansion of “the bad seed” should include constitutional genetic variants »
Hi yes I agree with MPort. I started taking Ruxilitinib with only the knowledge that it would shrink my spleen and help with itching, bone pain, night sweats etc. In my case it’s been mostly successful.It’s a very interesting article, it sounds like it’s pointing at patients nearing the transplant stage.
Thanks so much for posting this. Currently I have post Et Mf. I was diagnosed with fibromyalgia in my 30’s, arthritis in both my hips in my 40’s and then ET at age 52, back in 2008. I even had to quit teaching in my 40’s because of severe brain fog, weakness, and fatigue. It wasn’t until I found this site a few years ago that I found there might be a connection. It is an extremely interesting article and explains so much. Thanks again.
This is very interesting connection you described with MPN and fibromyalgia. Something I have been thinking, since me and my brother have both been diagnosed with CFS/ME. I also have ET. Can’t help to think that a common genetical weakness of the immune system could be feeding both of these inflammatory diseases.
Hello,i just read the article and i was a little bit confused: is the general feeling of this article so encouraging as you have written above in these sentences, or at some points in the end of it ("Unanswered Questions in MPN Inflammatory Pathophysiology and Treatment") suggest that things are very difficult to treat ("It is not clear whether a pro-apoptotic or anti-inflammatory approach can be successful, even in combination with ruxolitinib, hydroxyurea, or IFNα. In some secondary MF patients, active hematopoiesis derives almost exclusively from the malignant clone. An important question is whether in this set of patients, restoring benign hematopoiesis is possible"). I really got confused cause my English are not perfect so I might not understanding article correctly.I hope am wrong
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