TY - JOUR
T1 - A role for IFN-λ1 in multiple myeloma B cell growth
AU - Novak, A. J.
AU - Grote, D. M.
AU - Ziesmer, S. C.
AU - Rajkumar, V.
AU - Doyle, S. E.
AU - Ansell, S. M.
PY - 2008
Y1 - 2008
N2 - Multiple myeloma (MM) is a progressive disease that results from dysregulated proliferation of plasma cells. Although, causative factors such as genetic events and altered expression of anti-apoptotic factors have been described in a number of patients, the mechanistic details that drive myeloma development and continued growth of malignant cells remain largely undefined. Numerous growth factors, including interleukin (IL)-6, Insulin-like growth factor-1 and IL-10 have been shown to promote growth of MM cells suggesting a significant role for cytokines in this disease. Interferon (IFN)-λ1 is a new member of the Class II cytokine family that, similar to IFN-α, has been shown to mediate viral immunity. In light of data supporting a role for cytokines in myeloma, we investigated the significance of IFN-λ1 on myeloma cell biology. Our studies show for the first time that myeloma cells bind to soluble IFN-λ1, and that IFN-λ1 induces myeloma cell growth and protects against dexamethasone-induced cell death. Our data also show that IFN-λ1 induces phosphorylation of STAT1, STAT3 and Erk. Taken together, our results suggest that IFN-λ1 may regulate myeloma cell biology and could prove to be therapeutically important.
AB - Multiple myeloma (MM) is a progressive disease that results from dysregulated proliferation of plasma cells. Although, causative factors such as genetic events and altered expression of anti-apoptotic factors have been described in a number of patients, the mechanistic details that drive myeloma development and continued growth of malignant cells remain largely undefined. Numerous growth factors, including interleukin (IL)-6, Insulin-like growth factor-1 and IL-10 have been shown to promote growth of MM cells suggesting a significant role for cytokines in this disease. Interferon (IFN)-λ1 is a new member of the Class II cytokine family that, similar to IFN-α, has been shown to mediate viral immunity. In light of data supporting a role for cytokines in myeloma, we investigated the significance of IFN-λ1 on myeloma cell biology. Our studies show for the first time that myeloma cells bind to soluble IFN-λ1, and that IFN-λ1 induces myeloma cell growth and protects against dexamethasone-induced cell death. Our data also show that IFN-λ1 induces phosphorylation of STAT1, STAT3 and Erk. Taken together, our results suggest that IFN-λ1 may regulate myeloma cell biology and could prove to be therapeutically important.
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U2 - 10.1038/leu.2008.263
DO - 10.1038/leu.2008.263
M3 - Article
C2 - 18830264
AN - SCOPUS:57849093931
VL - 22
SP - 2240
EP - 2246
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 12
ER -