The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms

Abstract

Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated. Upregulation of HLA genes is considered one of the mechanisms of action of interferon (IFN)-alpha2, but regulation of these genes during IFN-alpha2 treatment in MPNs has never been studied. Our findings show a significant upregulation of several HLA genes of importance for tumor immune surveillance by IFN-alpha2 treatment in MPNs. This mechanism might enhance the cytotoxic potential of immune cells against MPNs and explain the induction of minimal residual disease by IFN-alpha2 treatment in these patients.

Keywords:

• Interferon-alpha2
• HLA genes
• whole blood transcriptional profiling
• myeloproliferative neoplasms
• tumor immune surveillance

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1262032.

Additional information

Funding

This work was supported by grants from Agnes og Poul Friis Fond, Civilingeniør Bent Bøgh og Hustru Inge Bøghs Fond, Steenbeck’s Legat, A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal, Fabrikant Einar Willumsens Mindelegat, Københavns Universitetsfond, Familien Hede Nielsens Fond.