Addiction to c-MYC in multiple myeloma

• Published in: Blood 2012-09, Vol.120 (12), p.2450-2453
• Main Authors: Holien, Toril, Våtsveen, Thea Kristin, Hella, Hanne, Waage, Anders, Sundan, Anders
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mesenchymal Stem Cells - drug effects; Multiple Myeloma - drug therapy; Multiple Myeloma - metabolism; Multiple Myeloma - pathology; Proto-Oncogene Proteins c-myc - antagonists & inhibitors; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Thiazoles - pharmacology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-08-371567

In multiple myeloma, c-MYC is activated and contributes to the malignant phenotype. Targeting MYC by short hairpin RNA induced cell death in myeloma cell lines; however, cell lines are generated from samples taken in advanced stages of the disease and may not reflect patient cells adequately. In this study, we used the selective small molecule inhibitor of MYC-MAX heterodimerization, 10058-F4, on myeloma cell lines as well as primary myeloma cells, and we show that inhibition of c-MYC activity efficiently induces myeloma cell death. Moreover, in cocultures of cell lines with bone marrow stromal cells from myeloma patients, the inhibitor still induces apoptosis. Our results provide further evidence that myeloma cells are addicted to c-MYC activity and that c-MYC is a promising therapeutic target in multiple myeloma.