Figure 7.

Summary of inflammatory pathway in the possible pathogenesis of MPN diseases. Initial inflammatory responses were largely mediated by TLR2 and less so by TLR4. Incorporating the S100A9/8 protein through MYD88 can induce NF-κB formation, producing inflammatory cytokines, and producing ROS and MDSC formation. Years of the chronic inflammatory process and accumulation of ROS formation induce DNA damage, then clonal evolution, including JAK2, setting up a vicious cycle of JAK2 mutation refractory to cytokine inhibition, producing more ROS, and leading to the formation of other genetic marker gene mutations, thereby causing the formation of myelofibrosis or leukemia.