Abstract
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 JAK2V617F 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.
Highlights
Myeloproliferative neoplasms (MPNs) occur as a result of clonal outgrowth of hematopoietic stem cells (HSCs) carrying a somatic mutation, most commonly in JAK2 (JAK2V617F ), endowing them with cytokine independent growth and ensuing in the overproduction of mature and differentiated cells of cells of the myeloid lineage [1,2,3,4,5]
MPNs are distinct from myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) which are characterized by arrested differentiation of progenitor cells leading to bone marrow failure and ineffective hematopoiesis
When former and current smokers were compared to never-smokers, there was a significant association between smoking history and the risk of MPN compared to chronic lymphoid leukemia (CLL) controls (Overall Risk (OR) = 1.73, 95% CI 1.25–2.40) [58]
Summary
Myeloproliferative neoplasms (MPNs) occur as a result of clonal outgrowth of hematopoietic stem cells (HSCs) carrying a somatic mutation, most commonly in JAK2 (JAK2V617F ), endowing them with cytokine independent growth and ensuing in the overproduction of mature and differentiated cells of cells of the myeloid lineage [1,2,3,4,5]. Myeloproliferative neoplasms (MPNs) are classic examples of chronic inflammation driven cancers where the inflammatory environment impacts disease initiation, symptomatology, and progression. Defining how risk factors impact MPN development will enable lifestyle modifications to improve patient outcomes in early stage of disease as well as to prevent MPN initiation in healthy individuals predisposed to developing MPN. In this review we will focus on the host components, lifestyle factors and environmental drivers of inflammation and their associated risk in MPN pathogenesis (Figure 1).
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