Dexamethasone induces apoptosis of multiple myeloma cells in a JNK/SAP kinase independent mechanism

Cytokine control of developmental programs in normal hematopoiesis and leukemia

“…Studies on normal and malignant lymphoid cells have shown that IL-1, IL-2, IL-4, IL-6, IL-7, and IL-9 suppress induction of apoptosis by dexamethasone (reviewed in Lotem and Sachs, 1999). IL-6 was also shown to suppress FAS-mediated apoptosis in normal hepatocytes (Kovalovich et al, 2001) and multiple myeloma cells (Chauhan et al, 1997) and IL-15 suppressed FASmediated apoptosis in normal mast cells and in mast cell lines (Masuda et al, 2001). Similar studies on neuronal cells have shown that induction of apoptosis by neurotoxic agents is suppressed by IL-6, NGF, BDNF, CNTF, and GDNF (reviewed in Lotem and Sachs, 1999).…”

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

“…Le Gouill et al (2004) have demonstrated that VEGF upregulates expression of antiapoptotic proteins, including myeloid cell leukemia, survivin, and cellular inhibitor of apoptosis protein. Furthermore, free bovine serum (starvation)-induced apoptosis in plasma cells is partially prevented by VEGF, confirming that this is a potent antiapoptotic cytokine in MM (Lichtenstein et al, 1995, Chauhan et al, 1997aTu et al, 2000).…”

The role of tumor necrosis factor α in the pathophysiology of human multiple myeloma: therapeutic applications

“…Our ®ndings also suggest that TNFa is secreted by MM cells, but that it is not a major MM growth factor. Our Chauhan et al, 1997Chauhan et al, , 2000Hideshima et al, 2000) and other (Borset et al, 1994;Lichtenstein et al, 1995;Catlett-Falcone et al, 1999) studies have demonstrated that IL-6 is the major growth and survival factor for human MM cells, and speci®cally shown that proliferation induced by IL-6 is mediated via the MAPK signaling pathway . The current study shows that TNFa-induced MM cell proliferation is also mediated via this cascade.…”

“…We Urashima et al, 1997;Chauhan et al, 1997Chauhan et al, , 2000 and others (Akira et al, 1990;Lichtenstein et al, 1995;Catlett-Falcone et al, 1999) have reported that IL-6 both induces proliferation of MM cells, mediated via the mitogen activated protein kinase (MAPK) cascade, and confers protection against dexamethasone (Dex)-induced apoptosis of MM cells, via speci®c activation of protein tyrosine phosphatase (SHP2). Others have shown that adhesion of MM cells to bone marrow stromal cells (BMSCs) confers protection against drug-induced apoptosis (Damiano et al, 1999), and we have shown that adherence of MM cells to BMSCs induces NF-kB dependent IL-6 transcription and secretion by BMSCs .…”