Impact of Host, Lifestyle and Environmental Factors in the Pathogenesis of MPN

Philadelphia-negative myeloproliferative neoplasms (MPNs) occur when there is over-production of myeloid cells stemming from hematopoietic stem cells with constitutive activation of JAK/STAT signaling, with JAK2(V617F) being the most commonly occurring somatic driver mutation. Chronic inflammation is a hallmark feature of MPNs and it is now evident that inflammation is not only a symptom of MPN but can also provoke development and precipitate progression of disease. Herein we have considered major MPN driver mutation independent host, lifestyle, and environmental factors in the pathogenesis of MPN based upon epidemiological and experimental data. In addition to the traditional risk factors such as advanced age, there is evidence to indicate that inflammatory stimuli such as smoking can promote and drive MPN clone emergence and expansion. Diet induced inflammation could also play a role in MPN clonal expansion. Recognition of factors associated with MPN development support lifestyle modifications as an emerging therapeutic tool to restrain inflammation and diminish MPN progression.