Interferon α extends the survival of human myeloma cells through an upregulation of the Mcl‐1 anti‐apoptotic molecule

We have recently reported that Mcl‐1, an anti‐apoptotic member of the Bcl‐2 family, is upregulated by interleukin (IL)‐6 in human myeloma cells through the janus kinase/signal transducers and activators of transduction (JAK/STAT) pathway. In the current study, we have explored the effects of interferon (IFN)‐α, a cytokine which has been shown to increase myeloma cell survival. Our results demonstrate that IFN‐α potently upregulates Mcl‐1 on both myeloma cell lines and purified native myeloma cells. Of note, this upregulation is not due to an induction of an IL‐6 autocrine loop. Furthermore, we showed that IL‐6 and IFN‐α had no additive effect on Mcl‐1 upregulation, suggesting that both cytokines act through a common mechanism. Finally, the analysis of signalling transduction pathways strongly suggests that Mcl‐1 upregulation induced by IFN‐α depends on STAT3 activation. Altogether, our data show that IFN‐α has an IL‐6‐like effect on human myeloma cells and suggest that it could be deleterious in some patients.