Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development

Abstract

Myeloproliferative neoplasms (essential thrombocythemia, ET; polycythemia vera, PV; myelofibrosis, MF) are monoclonal malignancies associated with genomic instability, dysregulated signaling pathways, and subsequent overproduction of inflammatory markers. Acknowledged for their debilitating symptom profiles, recent investigations have aimed to determine the identity of these markers, the upstream sources stimulating their development, their prevalence within the MPN population, and the role they play in symptom development. Creation of dedicated Patient Reported Outcome (PRO) tools, in combination with expanded access to cytokine analysis technology, has resulted in a surge of investigations evaluating the potential associations between symptoms and inflammation. Emerging data demonstrates clear relationships between individual MPN symptoms (fatigue, abdominal complaints, microvascular symptoms, and constitutional symptoms) and cytokines, particularly IL-1, IL-6, IL-8, and TNF-α. Information is also compiling on the role symptoms paradoxically play in the development of cytokines, as in the case of fatigue-driven sedentary lifestyles. In this paper, we explore the symptoms inherent to the MPN disorders and the potential role inflammation plays in their development.

Crucial factors of the inflammatory microenvironment (IL-1β/TNF-α/TIMP-1) promote the maintenance of the malignant hemopoietic clone of myelofibrosis: an in vitro study

“…Besides molecular abnormalities, the inflammatory microenvironment has emerged in the last few years as a key-player in MF pathogenesis [10]. Abnormal expression and activity of several cytokines involved in inflammation and immunoregulation are associated with MF [11] and correlate with more severe marrow fibrosis [12, 13], worsening systemic symptoms [14] and decreased survival [15].…”

Increased plasma nicotinamide phosphoribosyltransferase is associated with a hyperproliferative phenotype and restrains disease progression in MPN‐associated myelofibrosis

“…However, the molecular mechanisms underlying MPN-associated myelofibrosis are still not clear. JAK-STAT pathway activation is the main mechanism of myeloproliferation [3,4]; however, available evidence indicates that inflammatory/immune mechanisms play an important role in the phenotype of MPN-associated myelofibrosis by increased production of inflammatory cytokines and reduced number of regulatory T-cells [5][6][7][8][9][10]. From these considerations, it appears that understanding the mechanisms involved in the initiation and progression of MPNassociated myelofibrosis is a pivotal step for the generation of more effective therapeutic approaches.…”

The effectiveness of exercise-based rehabilitation to patients with myeloproliferative neoplasms-An explorative study

“…Thus, group exercise or frequent consultations with a health professional could perhaps heighten motivation. One might speculate, whether a stricter regime or 12 weeks of supervised exercising would increase adherence, and thereby result in a positive alteration of the cytokine milieu (especially interleukin 1 and 6, and tumour necrosis factorα, all associated with patient-reported outcomes (Geyer, Dueck, Scherber, & Mesa, 2015)), improvement of the We observed a significant increase in the physical capacity tests.…”

“…Thus, group exercise or frequent consultations with a health professional could perhaps heighten motivation. One might speculate, whether a stricter regime or 12 weeks of supervised exercising would increase adherence, and thereby result in a positive alteration of the cytokine milieu (especially interleukin 1 and 6, and tumour necrosis factor‐ α , all associated with patient‐reported outcomes (Geyer, Dueck, Scherber, & Mesa, )), improvement of the micro‐ and macrovascular components, and weight loss, ultimately leading to improvements in the MPN‐related symptoms including fatigue. We did, however, observe a small effect (Cohen’s d > 0.20) on physical fatigue measured by the MFI‐20, indicating some positive alteration of the perceived fatigue in the participants.…”