Death of multiple myeloma cells induced by cAMP-signaling involves downregulation of Mcl-1 via the JAK/STAT pathway

► We investigated the mechanisms whereby cAMP induces apoptosis in human multiple myeloma cells. ► Expression of the pro-survival protein MCL-1was rapidly and selectively reduced by cAMP. ► cAMP inhibited the JAK/STAT pathway which is known to regulate MCL-1 transcription. ► Exogenous IL-6 did not prevent cAMP-mediated inhibition of the JAK/STAT pathway or the cell death. ► Modulation of cAMP-signaling is a promising target for treatment of multiple myeloma.