Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation

Figure 2

Increased risk of myeloid malignancy in case of chronic inflammation. Chronic inflammation may be related to solid cancer or to other causes (infectious, toxic, and physical). In all cases the immune response includes an increased stimulation of the production of myeloid cells, with the associated increased risk of DNA alteration in dividing progenitor cells. Over the years, a myeloid progenitor may acquire a defect in a gene critical for survival or proliferation (MPL, JAK2, and CALR?) and a MPL-, JAK2-, or CALR-mutated malignant clone may expand and lead to a MPN. Other mutations providing a mild growth advantage (TET2, IDH1/2?) may occur before or after the MPL, JAK2, or CALR mutations. In the case of inflammation related to solid cancer, cancer cells and the inflammatory cytokines they produce likely affect immune cells.