Conclusion and perspectives
The MPNs are inflammatory cancers, in which the malignant clone per se generates inflammatory products that in a selfperpetuating vicious circle sustain the inflammatory drive and accordingly disease progression in the biological continuum from the early cancer stages (ET/PV) to the advanced Bburntout^ myelofibrosis stage and imminent leukemic transformation [120–128]. During this evolution, additional mutations, other than the driver mutations, emerge. The MPNs are associated with several Binflammatory^ co-morbidities, including an increased risk of second cancers [105–108], which are likely due to a defective tumor immune surveillance system being partly attributed to the chronic inflammatory state [108]. The cornerstone treatment of MPNs in the future is foreseen to be IFN-alpha2, which as monotherapy in several studies during the last three decades has demonstrated safety and efficacy and as the only agent within MPNs is able to induce MRD and accordingly being disease modifying [30, 31, 33, 41]. Thus, recently, the apparent disease-modifying potential of IFN-alpha2 in PV and ET as evidenced by the progressive reduction of the JAK2V617 tumor burden during prolonged therapy has elicited renewed efforts to evaluate its clinical efficacy as front-line therapy for early stage disease in terms of reducing thrombo-hemorrhagic events, normalization of biochemical, hematologic, and molecular variables, and, ultimately, altering the natural history of these diseases.
