MPN Workshop of the Carolinas 2025 | Mechanisms driving anemia in myelofibrosis and approaches under development for this complication

Well, anemia in myelofibrosis is not only very common, most patients will experience anemia during their disease course. It’s also prognostic, meaning that anemia is associated with a worse outcome for patients with myelofibrosis. But lastly, as you mentioned, it’s a very complicated mechanism. There’s not just one thing that causes anemia in these patients, it’s a multitude of things. It is the disease biology, mutations within the disease that cause dysfunctional erythropoiesis. There are a lot of cytokines that can alter things like hepcidin levels, leading to an inflammatory block on the production of red cells. The treatments that we use to treat myelofibrosis, such as JAK inhibitors, can slow down red cell production. Then often there’s increased destruction of red cells as well within the patient. So any given patient might have four different mechanisms of why they may be anemic. And there may be other factors that influence this as well. So really it’s a challenge to treat because you’re treating like four or five different problems all at once. So a single agent that acts in a single way may not totally fix the anemia in any given individual patient. 

So there’s been a lot of focus on the kind of the SMAD pathway within myelofibrosis. This is part of the NF-kappa-B signaling pathway. And whether we’re talking about luspatercept or hepcidin, they all kind of work in the same area, which is really exciting. Hepcidin itself is a very exciting thing because we’re manipulating hepcidin in different ways within the MPNs. In polycythemia vera, we’re manipulating hepcidin to lower red cell production. While in myelofibrosis, we’re doing the opposite. We’re manipulating hepcidin levels in order to increase red cell production. So that’s kind of a cool pathobiology approach that we’re using in myelofibrosis all in one, as well as PV all in one. But other drugs like luspatercept and elritercept are also working on this kind of SMAD pathway to improve red cell production so really that’s kind of the central focus right now but ultimately a lot of novel agents or new drugs that are being developed targeting different pathways are looking to root out the disease itself and if we can eliminate the myelofibrosis cells we can let the normal bone marrow grow back thus improving anemia in these patients

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.