Myc/max family of transcription factors and bcl-2 are involved in drug-induced apoptosis of myeloma cells.

Abstract

Cell homeostasis is controlled by a balance between proliferation, growth arrest and apoptosis. It is becoming increasingly evident that dysregulation of genes that control apoptosis contributes to the pathogenesis of disease such as cancer and autoimmune disease (1). In multiple myeloma, myeloma cells are terminally differentiated and fail to apoptose. Glucocorticoids such as dexamethasone (Dex) are often used in the treatment of myeloma, either alone or in combination with cytotoxic agents (2, 3). Similarly, IL-6 in the bone marrow environment protects immature myeloma cells form Dex-induced apoptosis (4). However, with prolonged treatment, patients develop resistance to these agents. It is well established that both glucocorticoids and chemotherapeutic drugs are potent inducers of cell death, by apoptosis (1). In fact, recent studies have demonstrated that Dex-induced apoptosis in several human myeloma cell lines and that interleukin-6 (IL-6), a B cell differentiation/survival factor, protected them from Dex-induced apoptosis (5, 6, Epstein J personal communication). The molecular mechanisms that govern these processes are not fully understood. Restoration of the apoptopic response in myeloma cells could lead to the development of effective therapy for multiple myeloma.