Phenotypes have revealed
another layer of heterogeneity in MF.1,2
Beyond recognizing the mutations that underscore the differences between primary and secondary myelofibrosis (MF), research has shown what else can be discovered about these patients at the phenotypic level (based on several factors, including peripheral blood cell counts).
As previously discussed, epigenetic mutations may drive disease initiation and progression, while splicing mutations may amplify cytopenias.1 If these mutations are present, your patient may display more attributes that are closer to the cytopenic phenotype.2
Cytopenias are an ever-changing challenge.
A main discerning feature between MF phenotypes is peripheral blood cell counts. The noncytopenic phenotype usually exhibits elevated/normal white blood cells and/or platelets, whereas the cytopenic phenotype often mimics a bone marrow failure state and may result in ineffective hematopoiesis.2
In these patients, anemia and thrombocytopenia are common clinical challenges in managing MF.7 These cytopenias are often present at diagnosis and generally increase over time, which further showcases the continued need for monitoring.8-10
In a study measuring anemia and RBC transfusion requirements8*:
‡Based on 807 physicians from 12 countries (60% EU, 25% US, 15% ex-US/EU) who completed surveys, 54% from academic centers and 46% from community-based centers. There were approximately 18,000 patients with MF in the US and 24,000 in the EU.10
The heterogeneous nature of MF requires a deeper look beyond any one pathway.2
Researchers continue to explore the heterogeneity of MF and the different phenotypes within the disease that may extend beyond the JAK-STAT pathway. These findings could evolve the management for patients with this challenging disease.
For example, the poor prognosis associated with cytopenic MF can be partly characterized by having triple-negative disease or low JAK2V617F allele burden, suggesting that the disease may be driven by complementary JAK-independent mechanisms.
Recent research has shown that pathways beyond JAK-STAT are likely playing a role in the inflammatory pathophysiology of primary MF, which may affect how this disease is managed.7,16