A role for IFN-λ1 in multiple myeloma B cell growth

被引:23
作者
Novak, A. J. [1 ]
Grote, D. M. [1 ]
Ziesmer, S. C. [1 ]
Rajkumar, V. [1 ]
Doyle, S. E. [2 ]
Ansell, S. M. [1 ]
机构
[1] Mayo Clin, Dept Med, Div Hematol, Rochester, MN 55905 USA
[2] Zymogenet Inc, Dept Hematol & Oncol, Seattle, WA 98105 USA
基金
美国国家卫生研究院;
关键词
myeloma; IL-29; IFN-lambda;
D O I
10.1038/leu.2008.263
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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)-lambda 1 is a new member of the Class II cytokine family that, similar to IFN-alpha, has been shown to mediate viral immunity. In light of data supporting a role for cytokines in myeloma, we investigated the significance of IFN-lambda 1 on myeloma cell biology. Our studies show for the first time that myeloma cells bind to soluble IFN-lambda 1, and that IFN-lambda 1 induces myeloma cell growth and protects against dexamethasone-induced cell death. Our data also show that IFN-lambda 1 induces phosphorylation of STAT1, STAT3 and Erk. Taken together, our results suggest that IFN-lambda 1 may regulate myeloma cell biology and could prove to be therapeutically important.
引用
收藏
页码:2240 / 2246
页数:7
相关论文
共 16 条
[11]
Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival [J].
Novak, AJ ;
Bram, RJ ;
Kay, NE ;
Jelinek, DF .
BLOOD, 2002, 100 (08) :2973-2979
[12]
Interferons, interferon-like cytokines, and their receptors [J].
Pestka, S ;
Krause, CD ;
Walter, MR .
IMMUNOLOGICAL REVIEWS, 2004, 202 :8-32
[13]
PLASMA-CELL LEUKEMIA WITH ALPHA-INTERFERON THERAPY IN MYELOMA [J].
SAWAMURA, M ;
MURAYAMA, K ;
UI, G ;
MATSUSHIMA, T ;
TAMURA, J ;
MURAKAMI, H ;
NARUSE, T ;
TSUCHIYA, J .
BRITISH JOURNAL OF HAEMATOLOGY, 1992, 82 (03) :631-631
[14]
IL-28, IL-29 and their class II cytokine receptor IL-28R [J].
Sheppard, P ;
Kindsvogel, W ;
Xu, WF ;
Henderson, K ;
Schlutsmeyer, S ;
Whitmore, TE ;
Kuestner, R ;
Garrigues, U ;
Birks, C ;
Roraback, J ;
Ostrander, C ;
Dong, D ;
Shin, J ;
Presnell, S ;
Fox, B ;
Haldeman, B ;
Cooper, E ;
Taft, D ;
Gilbert, T ;
Grant, FJ ;
Tackett, M ;
Krivan, W ;
McKnight, G ;
Clegg, C ;
Foster, D ;
Klucher, KM .
NATURE IMMUNOLOGY, 2003, 4 (01) :63-68
[15]
Westendorf JJ, 1996, LEUKEMIA, V10, P866
[16]
Novel interferon-λs induce antiproliferative effects in neuroendocrine tumor cells [J].
Zitzmann, Kathrin ;
Brand, Stephan ;
Baehs, Sebastian ;
Goeke, Burkhard ;
Meinecke, Jennifer ;
Spoettl, Gerald ;
Meyer, Heinrich ;
Auernhammer, Christoph J. .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 344 (04) :1334-1341