A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.

Michel Jourdan (1) , Jean-Luc Veyrune (1) , John De Vos (1) , Nicole Redal (1) , Guilhem Couderc (1) , Bernard Klein (1)

1 Immunopathologie des maladies tumorales et autoimmunes

Interleukin-6 (IL-6) is a major survival factor for malignant plasma cells involved in multiple myeloma. Using an RNase protection assay, we looked for gene expression of 10 anti- and proapoptotic Bcl-2-family proteins in 12 IL-6-dependent human myeloma cell lines (HMCL). A high Mcl-1 gene expression was found in all HMCLs and the other genes were variably expressed. Out of the 10 Bcl-2-family members, only the Mcl-1 gene was regulated by IL-6. Upon starvation of IL-6, Mcl-1 gene expression decreased in association with myeloma cell apoptosis and was upregulated after adding IL-6 again in association with myeloma cell survival. A constitutive Mcl-1 expression was induced with an Mcl-1-GFP retrovirus in two IL-6-dependent HMCLs. The Mcl-1 HMCLs have a marked reduced apoptosis upon IL-6 starvation compared to HMCLs transduced with control GFP retrovirus and may grow without adding IL-6. These data emphasize the major role of Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.

Mots clés: myeloma; IL-6; apoptosis; Mcl-1

Domaines: Biochimie, Biologie Moléculaire

Michel Jourdan, Jean-Luc Veyrune, John De Vos, Nicole Redal, Guilhem Couderc, et al.. A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.. Oncogene, 2003, 22 (19), pp.2950-9. ⟨10.1038/sj.onc.1206423⟩. ⟨inserm-00130855⟩