Growth control mechanisms in multiple myeloma.
Interleukin-6 (IL-6) is the major growth factor for the malignant plasma cell clone in patients with multiple myeloma (MM). Although interferon-alpha (IFN-alpha) has been widely used as maintenance therapy in MM, controversy exists as to its clinical utility. This review summarizes data showing that cell growth arrest brought about by type I (IFNs-alpha/beta) and type II (IFN-gamma) IFNs occurs in part through utilization/modification of various components of the otherwise stimulatory Jak-STAT and Ras signaling pathways triggered by IL-6. Recent experimental results indicating that IFN-alpha acts as a survival factor for certain myeloma cell lines and frequently induces endogenous IL-6 expression may help to explain the conflicting clinical findings obtained in this heterogeneous disease with this usually potent growth inhibitor. By comparison, consistent antiproliferative activity exhibited by IFN-gamma on IL-6-dependent myeloma cell lines and primary myeloma cells from patients suggests that further investigation of the possible value of this cytokine in the treatment of MM may be warranted.
Hawley
R G
RG
Oncology Gene Therapy Program, The Toronto Hospital, Ontario, Canada.
Berger
L C
LC
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use; D015850:Interleukin-6 / Q000502:physiology*; D009101:Multiple Myeloma / Q000473:pathology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000502:physiology
D007155:Immunologic Factors; D016898:Interferon-alpha; D015850:Interleukin-6; D009363:Neoplasm Proteins; D007371:Interferon-gamma; D018631:ras Proteins