The bidirectional relationship between JAK2V617F allele burden and inflammation in polycythaemia vera: Insights from interferon and ruxolitinib therapy

Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal hematopoietic stem cell disorders driven by recurrent mutations in JAK2, CALR, or MPL, resulting in constitutive activation of the JAK–STAT signaling pathway. Although these mutations are central to disease initiation, accumulating evidence indicates that chronic inflammation plays a pivotal role in disease progression and clinical manifestations, making it a relevant therapeutic target.1 In PV, the interplay between inflammation and clonal hematopoiesis appears particularly important as inflammatory signals may promote the expansion and persistence of the JAK2V617F mutant clone, thereby influencing its accumulation over time. Within this context, the two principal targeted agents, pegylated interferon‐α and ruxolitinib, both exert anti‐inflammatory effects. Interferon therapy in PV evolved from conventional and pegylated IFN‐α2a to ropeginterferon alfa‐2b (Ropeg), a long‐acting formulation that enables sustained treatment while preserving disease‐modifying activity. Recent data indicate that ropeginterferon and ruxolitinib differ in clonal suppression, likely due to distinct interactions with the inflammatory microenvironment, providing the rationale for this brief review of their biological and therapeutic implications