Myeloproliferative neoplasms have a prevalence of around 350,000 in the USA and include the diagnoses of essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). These clonal neoplasms share core set of acquired driver mutations in JAK2, calreticulin (CALR), and MPL which all lead to constitutive activation of the JAK-STAT pathway. Additionally, a range of somatic mutations may occur which impact disease phenotype as risk of progression (such as ASXL1, IDH 1 & 2, EZH2 2 etc). The burden of these illnesses include a predisposition to thrombosis or bleeding, a range of challenging symptoms (from spleen pain, to hypermetabolic symptoms, pruritus, fatigue, bone pain), splenomegaly, cytopenias, and potential progression to acute myeloid leukemia. Although the origin of these diseases are anchored in a clonal neoplastic process, inflammation potentially plays a role in the risk of thrombosis, the origin of many of the difficult symptoms, potential contribution to cytopenias, and the potential risk of progression from ET/PV to MF, or from MF to AML. A spectrum of cytokines have been found to be elevated in MPNs (especially in MF), with elevation of certain ones negatively impacting prognosis including IL-8, IL-2R, IL-12, IL-15. Therapy of MPNs now includes non-specific cytoreduction (i.e. hydroxyurea for ET-PV), long acting interferons (i.e. ropegylated interferon a2b for polycythemia vera), and JAK inhibition with ruxolitinib (inhibits JAK1 and JAK2), fedratinib (JAK2 and FLT3), pacritinib (inhibits JAK2, FLT3, IRAK1, and ACVR1), and momelotinib (inhibits JAK1, JAK2, ACVR1). The JAK inhibitors have made a significant impact on decreasing the burden MPN patients face by decreasing splenomegaly (and its associated symptom burden), by decreasing MPN associated symptoms, and by improving survival. The mechanism of improved survival is not fully understood but may include a decrease in marrow inflammation and perhaps decreasing the mutagenic pressure that leads to additional somatic mutations such as ASXL1 that leads to AML. Hepcidin associated with inflammation is dually being investigated as means to decrease erythrocytosis in PV with hepcidin mimetics (i.e. rusferatide), and to improve MF associated anemia by inhibiting hepcidin (momelotinib or pacritinib by ACVR1 inhibition). Inflammation as both a driver of disease burden and progression, as well as a viable therapeutic target remains an important focus of investigation and interventional trials.

Citation Format: Ruben Mesa. Myeloproliferative neoplasms: Inflammation and treatment [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr IA22.