Over the past decade, myeloproliferative neoplasms (MPNs) have moved from being viewed as indolent chronic disorders to paradigmatic models of clonal haematopoiesis, vascular injury and systemic inflammation. In RiseMPN 2025 we explored this evolving landscape by focusing on inflamed vessels and clonal survival: how “fire in the blood” and niche remodeling shape thrombosis, fibrosis and disease progression. That meeting asked why disease trajectories diverge. RiseMPN 2026 will ask a bolder question: Can we engineer disease trajectories in MPNs?
The therapeutic toolkit in MPNs is expanding rapidly. JAK inhibition has transformed symptom control and splenomegaly, but has only partially delivered on the promise of disease modification. At the same time, a new generation of agents is emerging: interferons and other immunomodulators; anti-inflammatory and anti-fibrotic approaches; hepcidin and activin-ligand–targeting drugs; epigenetic and transcriptional modulators; p53/MDM2 and BCL2 family inhibitors; rational antithrombotic and cardiometabolic strategies. The central challenge for the next decade is no longer merely what works, but which combinations, in which patients, at which time-point, can genuinely rewrite the natural history of disease.
RiseMPN 2026 is designed as a translational dialogue across three axes: Mechanism → Combination → Trajectory. First, we will map the pathway constellations that matter most for synergy – from JAK/STAT and inflammatory signalling to metabolic stress, niche reprogramming and immune escape. Second, we will critically appraise emerging combination strategies in MF, PV and ET, moving beyond single-agent narratives to consider how layering therapies can achieve fibrosis regression, molecular clearance, vascular protection and durable haematologic remissions. Third, we will confront the strategic questions that increasingly shape daily practice: early versus delayed intensification, add-on versus switch, integration with allogeneic transplant, and the role of real-world data and AI-driven models in guiding these choices.
Central to this discussion is the need to define what we mean by “disease modification” in MPNs. Across the programme we will revisit our endpoints: from spleen volume and symptom scores to dynamic measures of allele burden, bone marrow architecture, clonal competition, cardiovascular risk and quality of life. We will examine how to design disease-modifying trials, how to read intermediate signals along a trajectory, and how to balance efficacy, safety, cost and feasibility in a field where many patients will never see a transplant but all deserve a rational long-term plan.
RiseMPN 2026 therefore aims to be more than an update meeting. It is an invitation to the MPN community to think and act as “trajectory engineers”: to integrate mechanism with clinical reality, combination design with strategic positioning, and innovative endpoints with meaningful benefit for patients. By bringing together basic scientists, translational researchers, trialists, transplant physicians, cardiologists and young investigators around a single guiding question – “Can we engineer disease trajectories in MPNs?” – we hope to co-create the conceptual and practical framework that will define the next era of MPN care.
