Abstract
Abstract
Cytokines serve vital roles in the regulation of immune responses. In patients diagnosed with hematologic malignancies, cytokines may play a role in the tumor-host microenvironment affecting tumor survival and progression. Previous studies have quantified the variation in cytokine concentrations between malignant and normal states in patients’ serum. However the research is sparser in relation to measurement of cytokine concentrations in the bone marrow microenvironment. Multiple myeloma (MM) and Waldenström's macroglobulinemia (WM) are two such malignancies that arise in the B-lymphoid lineage and proliferate within the bone marrow (BM) microenvironment. In this study, an ultra-sensitive IL-6 and a human TH1/TH2 multiplex ELISA system were utilized to determine protein concentrations of the following cytokines: IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, IL-13, IFN-gamma, and TNF-alpha, in the BM supernatant and peripheral blood (PB) of 20 patients with WM, 16 patients with MM, and 7 controls. The BM supernatant concentration of TNF-alpha was significantly increased in MM compared to controls (10.650 pg/ml vs. 4.980 pg/ml, p=0.0158). IL-1beta was significantly decreased in the bone marrow supernatant of MM (0.038 pg/ml vs. 2.352 pg/ml, p=0.0469) and WM (0.046 pg/ml vs. 2.352 pg/ml, p=0.0435). IL-8 was also significantly decreased in the BM supernatant of patients with MM (11.520 pg/ml vs. 43.590 pg/ml, p=0.0158) and WM (7.348 pg/ml vs. 43.590 pg/ml, p=0.0036). Differences in BM supernatant concentrations of IL-6 were not significant in MM, WM, and normal controls. Analysis of PB showed IL-2, IL-5, IL-6, IL-8, IL-10, and TNF-alpha were significantly increased in both MM and WM versus controls, and IFN-gamma was significantly increased in WM. Hierarchical clustering analysis of the cytokine profiles suggested two distinct subgroups existed within both MM and WM. TNF-alpha was the only cytokine in our study that was increased in both the bone marrow and serum of MM patients. The discordant results obtained in the BM supernatant vs. PB for IL-6 and IL-8 in both MM and WM indicate that cytokine profiles vary somewhat between the PB and BM compartments. The BM supernatant and PB cytokine profiles in patients with MM and WM highlight the important role cytokines may play in the microenvironment and biology of MM and WM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 802. doi:10.1158/1538-7445.AM2011-802
