Expression of the IFNAR1 chain of type 1 interferon receptor in benign cells protects against progression of acute leukemia

Abstract

Type I interferons (IFN) were widely used for leukemia treatment. These cytokines act on cell surface receptor consisting of the IFNAR1/2 chains to induce anti-tumorigenic effects. Given that levels of IFNAR1 can be regulated by phosphorylation-driven ubiquitination and degradation that undermines IFN signaling and anti-tumorigenic effects, we sought to determine the importance of IFNAR1 downregulation in progression of acute leukemia. Using knock-in mice deficient in downregulation of IFNAR1, we uncovered that IFNAR1 expression in stromal benign cells functions to protect against progression of leukemia. We discuss putative mechanisms of this regulation and potential of therapeutic targeting of IFNAR1 downregulation to treat leukemia.

Keywords:

• Acute leukemia
• interferon
• IFNAR1
• BCR-ABL

Acknowledgments

We thank Veronika Sexl and Warren Pear for reagents and critical suggestions.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1319053.

Additional information

Funding

The authors report no conflicts of interest. This work was supported by the NIH/NCI PO1 CA165997 and RO1 CA092900 grants (to S.Y.F.).