Interleukin-1β, JAK2V617F mutation and inflammation in MPNs

Long before the discovery of the JAK2, CALR, and MPL mutations, chronic inflammation was an established characteristic of BCR-ABL–negative myeloproliferative neoplasms (MPNs). Numerous studies showed that various conditions of chronic inflammation could precede and facilitate the development of all subtypes of MPNs. A nonexhaustive list of such conditions includes inflammatory bowel diseases, inflammatory rheumatic or autoimmune diseases, obesity, diabetes mellitus and not least, cigarette smoking.1-7 Cellular sources of production of proinflammatory cytokines include hematopoietic progenitors, especially megakaryocytes, typically mutated in MPNs, but also T-lymphocytes and endothelial cells, rarely mutated in MPNs, and stromal cells, which remain wild-type. The extent to which MPN-driver mutations contribute to the high level of inflammation characteristic of MPNs remains debated.