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 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.
Puthier
D
D
INSERM U463, Institut de biologie, and Departement d'Hématologie, CHU Nantes, Nantes, France.
Thabard
W
W
Rapp
M
M
Etrillard
M
M
Harousseau
J
J
Bataille
R
R
Amiot
M
M
D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D015850:Interleukin-6; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators