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Anti‐tumour activity of interferon‐alpha in multiple myeloma: role of interleukin 6 and tumor cell differentiation
Author(s) -
Matsui William,
Huff Carol Ann,
Vala Milada,
Barber James,
Smith B. Douglas,
Jones Richard J.
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04255.x
Subject(s) - clonogenic assay , cytokine , alpha interferon , cancer research , multiple myeloma , cell culture , cell growth , alpha (finance) , immunology , interleukin , cellular differentiation , biology , interferon , medicine , biochemistry , construct validity , nursing , patient satisfaction , gene , genetics
Summary. Interferon‐alpha (IFN‐α) is a pleotropic cytokine that has clinical activity against a wide variety of malignancies, including multiple myeloma (MM). In vitro , IFN‐α has diverse effects on both normal and malignant cells, however, the exact mechanisms responsible for its clinical anti‐tumour activity remain unclear. We found that IFN‐α inhibited MM cell proliferation in association with cell cycle arrest at G 1 and limited the clonogenic growth of both MM cell lines and primary patient specimens. At the doses tested, IFN‐α was not cytotoxic, but induced terminal plasma cell differentiation resulting in the loss of clonogenicity. These activities were markedly enhanced by the major MM growth factor interleukin 6 (IL‐6). Moreover, IL‐6 was required for this process, as neutralizing antibodies against IL‐6 inhibited the effects of IFN‐α. IL‐6 also induced MM cell terminal differentiation when combined with a second, unrelated, antiproliferative agent bryostatin‐1, suggesting that its differentiating activities are preferentially enhanced in the presence of agents that inhibit cell cycling. These results suggest that the differentiating activities of IFN‐α may play a role in its clinical antimyeloma activity and provide the rationale for clinical differentiation therapy in MM.