Early Intervention of Inflammation May Be Key in Myeloproliferative Neoplasms

With recent evidence pointing to a link between chronic inflammation and Philadelphia-negative myeloproliferative neoplasms, essential thrombocythemia, polycythemia vera, and myelofibrosis, Hans Carl Hasselbalch, MD, DMSc, and Mads Emil Bjorn, MD, PhDc, Department of Hematology, Roskilde Hospital, University of Copenhagen, Denmark, recently published a review article purporting that myeloproliferative neoplasms are inflammatory diseases.

"The concept of chronic inflammation as a major driver of disease progression in myeloproliferative neoplasms opens the avenue for clinical trials in which the 2 most promising agents within myeloproliferative neoplasms-interferon (IFN) and ruxolitinib-are combined and instituted in the early disease stage according to the early intervention concept," they explained. "The ability of IFN to induce deep molecular responses with normalization of the bone marrow, even years after cessation of IFN, and the role of inflammation in the initiation and progression of [myeloproliferative neoplasms] make the combination of IFN and ruxolitinib one of the most promising new treatment strategies for patients with [myeloproliferative neoplasms]."

In their article, the authors review evidence supporting the relationship between cancer and chronic inflammation, as well as evidence that myeloproliferative neoplasms are inflammatory and immune-deregulated diseases. For example, they discuss abnormal expression and activity of proinflammatory cytokines associated with myeloproliferative neoplasms, including the dysregulation of several immune and inflammation genes. Epidemiologic, histomorphologic, and clinical data are also reviewed. Clinical research points to inflammation-mediated cardiovascular and thromboembolic disease burden, chronic kidney disease, autoinflammatory diseases, as well as osteopenia and second cancers. Specifically, chronic inflammation has been associated with premature atherosclerosis, as well as the development of other hematologic and nonhematologic cancers in myeloproliferative neoplasms.

Dr Hasselbalch and Dr Bjorn also discuss biochemical evidence supporting the link between cancer and chronic inflammation and molecular data, and describe in detail the consequences of a Human Inflammation Model for Cancer Development . Furthermore, the consequences of chronic inflammation in myeloproliferative neoplasms are discussed, including chronic inflammation in the bone marrow, spleen, and circulatory system.

Lastly, focusing on therapy options, the authors suggest it may be necessary to rethink current approaches to care. In particular, early intervention with IFN-alpha2 therapy in combination with potent anti-inflammatory agents may be promising treatment options in the future.

Reference

Hasselbalch HC, Bjorn ME. MPNs as inflammatory diseases: the evidence, consequences, and perspectives. Mediators Inflamm. 2015;2015:102476.