IFN-γ binds TPO to inhibit hematopoiesis

Abstract

In this study, Alvarado et al1 (in the research group of Andre Larochelle) shed light on the mechanism of pancytopenia in inflammation, a long-standing clinical observation lacking an explanation. Interferon-γ (IFN-γ), a mediator of the inflammatory response, decreases hematopoietic stem and progenitor cell (HSPC) function by binding to thrombopoietin (TPO), thereby preventing it from signaling via its own receptor, c-MPL. This same understanding provides insight into how the TPO mimetic eltrombopag (ELT) can overcome IFN-γ-mediated inhibition of hematopoiesis, because it is unaffected by IFN-γ binding and, thus, can engage c-MPL and induce downstream signaling.