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

Abstract : 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)-alpha, a cytokine which has been shown to increase myeloma cell survival. 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. Furthermore, we showed that IL-6 and IFN-alpha 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-alpha depends on STAT3 activation. Altogether, our data show that IFN-alpha has an IL-6-like effect on human myeloma cells and suggest that it could be deleterious in some patients.
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https://hal-amu.archives-ouvertes.fr/hal-01595829
Contributor : Lionel Spinelli <>
Submitted on : Wednesday, September 27, 2017 - 9:28:36 AM
Last modification on : Tuesday, March 17, 2020 - 3:13:10 AM

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  • HAL Id : hal-01595829, version 1

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Denis Puthier, W. Thabard, M. Rapp, M. Etrillard, J. Harousseau, et al.. Interferon alpha extends the survival of human myeloma cells through an upregulation of the Mcl-1 anti-apoptotic molecule. Br. J. Haematol., 2001, 112 (2), pp.358--363. ⟨hal-01595829⟩

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