N-cadherin is a therapeutic target in t(4;14)-positive multiple myeloma

e238 Patients and Methods: CXCL9 serum levels were studied by ELISA in newly-diagnosed (ND) MM (n1⁄4105) and MGUS patients (n1⁄417), and healthy donors (n1⁄437). CXCL9 expression was analyzed by qPCR in MM cell lines (HMCLs), MM-BMMNCs, MM-PBMCs and in a publically available GEP-dataset (GSE2658). Concurrent analysis of CXCL9-11 serum levels was performed by FACS-CBA array. Results:Median CXCL9 levels (161 pg/ml; range: 9-1966) were significantly elevated in MM patients compared to MGUS (93; 6-1303) and healthy donors (106; 51e391). CXCL9 levels significantly correlated with B2M, ISS stage, calcium, albumin, LDH, hemoglobin and age. High CXCL9 levels predicted adverse survival (17.0 months vs. not reached, Pu003c0.001), which was upheld when age-adjusted cut-off levels were used. Similarly, in MM patients (n1⁄4559) treated within the TT2 and 3 protocol (GSE2658) shorter OS was found in patients with a present compared to those with an absent detection call for CXCL9 (P1⁄40.004). Expression of CXCL9 was only detected in 1 of 7 HMCLs and 12% of previously published MM cell samples. Hence, increased serum levels of CXCL9 are likely derived from other cell types. We observed increased expression of CXCL9 in PBMCs compared to BMMNCs of MM patients, suggesting that elevated secretion of CXCL9 might result from aberrant cytokine production in cells of the PB. CXCL9 serum levels were also analyzed in conjunction with CXCL10 and 11 in 65 MM patients by FACS-CBA. Again, we observed a significant correlation with B2M for CXCL9-11. Survival was significantly worse in patients with high compared to low CXCL9 (median OS 25.3 months vs. not reached, P1⁄40.003) and CXCL10 (19.97 months vs. not reached, P1⁄40.0006). In multivariate analysis, CXCL9 (P1⁄40.03) and CXCL10 (P1⁄40.013) were revealed as independent predictors of survival. Conclusion: Our findings depict CXCL9 as novel prognostic marker for overall survival in ND-MM patients. High levels of CXCL9 in the PB probably increase TH1/TH2 ratios and may shield myeloma cells from immune attack by CD8+ cytotoxic T cells as previously shown for T cell lymphomas. Further experiments will aim to confirm these results and define the functional role of CXCL9 in MM.