Researchers have uncovered how chronic inflammation contributes directly to abnormal blood cell development in two serious blood cancers, myelofibrosis (MF) and essential thrombocythemia (ET). The study, which examined patient plasma and stem cell cultures, suggests that inflammatory molecules circulating in the blood may worsen disease symptoms and points to new opportunities for targeted therapy.
Cytokines Amplify Megakaryocyte Growth
MF and ET belong to a group of conditions known as chronic myeloproliferative neoplasms, characterised by excessive production of blood cells driven by genetic mutations in the JAK2 pathway. However, the new research highlights that inflammation plays an equally critical role. When plasma from 30 MF and 28 ET patients was mixed with healthy cord-blood stem cells, scientists observed marked differences in cell behaviour.
Plasma from MF patients triggered an increase in megakaryocyte production, the bone marrow cells that generate platelets. This effect was reduced in samples from patients receiving the JAK inhibitor ruxolitinib, commonly used to treat MF. Further laboratory tests showed that blocking three key signalling routes, JAK1/2, MAPK and NF-kB, halted the abnormal cell growth, confirming all were involved. Raised levels of two inflammatory cytokines, interleukin-1β (IL-1β) and interleukin-6 (IL-6), closely matched increased megakaryocyte output, and using antibodies to block them reversed the effect.
A Different Mechanism in Essential Thrombocythaemia
In contrast, plasma from ET patients enhanced the formation of proplatelets, the precursors to platelets, along with higher activity of proteins NFE2 and Bcl-xL. The team also identified increased levels of the chemokine RANTES, which was linked to the abnormal platelet formation. Blocking the RANTES receptor CCR5 with the drug Maraviroc reduced this effect, suggesting that RANTES acts as a major driver in ET pathology.
Implications for Targeted Treatments
The findings clarify how specific inflammatory mediators shape different disease patterns in MF and ET. By integrating cytokine profiling with genetic data, doctors may eventually predict disease progression more accurately and tailor therapies that target both genetic and inflammatory drivers of these disorders.
Reference
Yañuk DB et al. Inflammatory mediators differentially regulate megakaryopoiesis and thrombopoiesis in myelofibrosis and essential thrombocythemia. Scientific Reports. 2025;15:43716.
