Interferon alpha 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 throug h the janus kinase/signal transducers and activators of transduction (JAK/S TAT) pathway. In the current study, we have explored the effects of interfe ron (IFN)-alpha, a cytokine which has been shown to increase myeloma cell s urvival. Our results demonstrate that IFN-alpha 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. Further more, we showed that IL-6 and IFN-alpha had no additive effect on Mcl-1 upr egulation, suggesting that both cytokines act through a common mechanism. F inally, the analysis of signalling transduction pathways strongly suggests that Mcl-1 upregulation induced by IFN-alpha depends on STAT3 activation. A ltogether, our data show that IFN-alpha has an IL-6-like effect on human my eloma cells and suggest that it could be deleterious in some patients.