Molecular characterization underlying IFN-α2 treatment in polycythemia vera: a transcriptomic overview.

Abstract

Polycythemia vera (PV) is the most common chronic myeloproliferative neoplasm (MPN) in adults. Pegylated interferon-α2 (IFN-α2) is an effective and safe drug for the treatment of PV. However, the mechanisms of its action in PV are still not fully understood. Using the WGCNA and Limma algorithm, we found a subset of IFN-α2 sensitive genes and four gene co-expression modules. Meanwhile, we also found 820 genes were differentially expressed in PV compared with healthy controls. By integrating the above results, several differentially expressed genes (DEGs) that were up- or down-regulated in PV but showed opposite alterations in the IFN-α2-treated group were found. These genes were mainly related to three types of biological processes (metal ion homeostasis, metabolic/catabolic process, and Jak-STAT signaling pathway), the dysfunctions of which were prevalent in PV. Moreover, we applied another threshold-free analysis method to compare global gene expression between IFN-α2 treated PV, PV, and control groups. Results showed the transcriptome changes of PV versus controls were negatively correlated with that of IFN-α2 treated versus untreated PV, indicating IFN-α2 treatment could partially reverse the dysregulated gene expression profile due to PV pathology. In summary, interferon may alleviate the progression of PV through multiple pathways. The findings may be of assistance in understanding the molecular basis underlying this treatment.