Growth Control Mechanisms in Multiple Myeloma

Abstract

Interleukin-6 (IL-6) is the major growth factor for the malignant plasma cell clone in patients with multiple myeloma (MM). Although interferon-α (IFN-α) 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-α/β) and type II (IFN-γ) 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-α 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-γ 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.

Key Words:

• Multiple myeloma
• interleukin-6
• interferons-α/β
• interferon-γ
• growth regulation