Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer?

Hans Hasselbalch1,*

1Department of Hematology, Roskilde Hospital, University of Copenhagen, Copenhagen, Denmark

The morbidity and mortality of patients with the chronic Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis are mainly caused by cardiovascular diseases, thrombohemorrhagic complications, and bone marrow failure because of myelofibrosis and leukemic transformation.In the general population, chronic inflammation is considered of major importance for the development of atherosclerosis and cancer. MPNs are characterized by a state of chronic inflammation, which is proposed to be the common denominator for the development of “premature atherosclerosis,” clonal evolution, and second cancer in patients with MPNs. Chronic inflammation may both initiate clonal evolution and catalyze its expansion from early disease stage to the myelofibrotic burnt-out phase. Furthermore, chronic inflammation may also add to the severity of cardiovascular disease burden by accelerating the development of atherosclerosis, which is well described and recognized in other chronic inflammatory diseases.A link between chronic inflammation, atherosclerosis, and second cancer in MPNs favors early intervention at the time of diagnosis (statins and interferon-alpha2 (IFN)), the aims being to dampen chronic inflammation and clonal evolution and thereby also diminish concurrent disease- mediated chronic inflammation and its consequences (accelerated atherosclerosis and second cancer) . In the context of “The Platelet-Cancer Loop” normalization of elevated platelets counts by IFN may be of particular importance to minimize the increased cancer invasiveness and metastatic potential which is associated with cancer-associated thrombocytosis in the general population and likely also in patients with MPNs and second cancer. In this perspective IFN and a statin may be a rational combination therapy to be used in the future, taking into account that both agents impair MPN-cell growth and statin treatment – in addition – has been shown to reduce cancer-related mortality as well.

Keywords: Cancer, Inflammation