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?

• Published in: Blood Vol. 119; no. 14; pp. 3219 - 3225
• Main Author: Hasselbalch, Hans Carl
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 05-04-2012; Americain Society of Hematology
• Subjects: Atherosclerosis (general aspects, experimental research); Atherosclerosis - epidemiology; Atherosclerosis - etiology; Atherosclerosis - metabolism; Autoimmunity; Biological and medical sciences; Blood and lymphatic vessels; Bone Marrow Neoplasms - etiology; Bone Marrow Neoplasms - metabolism; Cardiology. Vascular system; Chronic Disease; Clonal Evolution; Diabetes Mellitus - etiology; Disease Progression; Diseases of red blood cells; Hematologic and hematopoietic diseases; Humans; Hyperuricemia - etiology; Inflammation - complications; Inflammation - metabolism; Insulin Resistance; Kidney Diseases - etiology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Monocytes - metabolism; Morbidity; NF-kappa B - metabolism; Polycythemia Vera - complications; Polycythemias; Primary Myelofibrosis - complications; Signal Transduction; Thrombocythemia, Essential - complications; Clonality; Myelofibrosis; Hematology; Cardiovascular disease; Polycythemia vera; Malignant hemopathy; Inflammation; Malignant tumor; Vascular disease; Myeloproliferative syndrome; Essential thrombocythemia; Chronic; Second cancer; Atherosclerosis; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-11-394775

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-α2), 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).