Great advances have been made in our understanding of how myeloproliferative neoplasms (MPNs)–essential thrombocythemia, polycythemia vera, myelofibrosis (MF)–result in overproduction of inflammatory markers, according to Holly L. Geyer, MD, Assistant Professor of Medicine, Division of Hospital Internal Medicine, Mayo Clinic, Scottsdale, AZ, and colleagues.
As part of a review study, the authors explored the role inflammation plays in MPN pathobiology, disease advancement, and symptom development. In particular, they discussed characterization of MPN symptoms, as it is the most recognizable feature of the disease process and may contribute to decreased life expectation. Fatigue, early satiety, and abdominal pain are but a few of the multitude of prominent symptoms patients with this condition face.
Research has focused on determining the scope and extent of MPN symptoms. To that end, several tools have been developed, including the MF Symptom Assessment Form, the MPN Symptom Assessment Form, and the MPN Symptoms Assessment Score.
In addition, Dr Geyer and colleagues reviewed the different origins of inflammation in patients with MPN. The mechanism of action for inflammation among healthy patients involves cellular responses and neurohormonal stimulatory factors and cytokines; dysregulation of this system is the key feature of MPN. Studies have evaluated the role of members of the Janus kinase signal transduction, as well as the role of the Janus kinase cascade, and STAT transcription factors. The authors also discuss the role of chronic inflammation in patients with MPN, including the role of DNA damage, cellular remodeling, and fibrosis.
The relationship between inflammation and symptom development in MPN are also discussed in the review. For example, Dr Geyer and colleagues cite research evaluating the role of abnormal cytokine expression within MF, assessing the link between cytokines and MF symptoms, as well as research evaluating specific combinations of inflammatory markers. Furthermore, the review provides detailed information about research conducted about specific MPN symptoms, and how they are related to inflammation, including fatigue, splenomegaly, microvascular, cognitive symptoms, and pruritus, as well as constitutional symptoms.
Lastly, the authors of the review discuss ways of improving MPN symptoms by targeting specific cytokines, including reducing fat intake and increasing physical activity. Researchers have also evaluated inhibiting JAK2 as a means to prevent cytokine dysregulation, as well as the impact of JAK2 inhibitors, including momelotinib and pacritinib.
"Clear relationships exist between MPN symptoms and markers of inflammation," Dr Geyer and colleagues concluded."
Though most data remains in early stages of investigation, knowledge gleaned from other malignancies has offered us potential mechanisms that explain these observed cytokine-symptom associations."
Geyer HL, Dueck AC, Scherber RM. Impact of inflammation on myeloproliferative neoplasm symptom development. Mediators Inflamm. 2015;2015:284706.