Immune and cytokine landscape differs between cytopenic and proliferative phenotypes in primary myelofibrosis
Sze-Hwei Lee, Yu-Hung Wang, Yu-Sung Chang, Chao-Hung Wei, Chang-Tsu Yuan, Hsin-An Hou, Wen-Chien Chou, Hwei-Fang Tien, Chien-Chin LinBackground
Cytopenia represents a distinct clinical phenotype in primary myelofibrosis (PMF), often associated with advanced disease and poor prognosis. We propose that while a common driver mutation initiates the disease, the clinical phenotype of PMF is shaped by inter-individual variability in downstream inflammatory responses, contributing to the observed heterogeneity in disease presentation.
Objectives
To characterize inflammatory and immune signatures distinguishing cytopenic from proliferative phenotypes of PMF.
Design
Retrospective, single-center observational study analyzing clinical, molecular, transcriptomic, and cytokine data from patients with pathologically confirmed PMF.
Methods
We analyzed a cohort of 140 patients with PMF, stratified into cytopenic and proliferative phenotypes based on abnormalities in at least one peripheral blood lineage. Bone marrow transcriptomic profiling was performed using the NanoString nCounter PanCancer Immune Panel. Cytokine levels were measured by MILLIPLEX® bead-based multiplex assay, and phosphorylated NFκB p65 expression was evaluated by immunohistochemistry.
Results
Compared with the proliferative phenotype, cytopenic PMF showed more advanced disease features, including higher blast counts (P<0.001), elevated LDH (P<0.001), and more frequent overt fibrosis (P<0.001). Cytopenic patients had fewer
Conclusion
Our findings highlight cytopenic PMF as a biologically distinct and clinically aggressive phenotype characterized by inflammatory pathway activation, particularly involving NFκB signaling and elevated IL-8. These results support the role of immune dysregulation in the pathogenesis of cytopenia in PMF and provide a basis for further investigation into its clinical implications.