Abstract. The objective of the present study was to evaluate the prognostic values of platelet count (PLT) and platelet to lymphocyte ratio (PLR) in diffuse large B-cell lymphoma (DLBCL), creating a novel prognostic scoring system. A total of 309 patients with newly diagnosed DLBCL were retrospectively analyzed. Receiver operating characteristic analysis was used to determine the optimal threshold values for PLT and PLR, which were 250x10 9 /l and 170, respectively. The patients with PLT ≥250x10 9 /l and PLR ≥170 experienced significantly decreased overall survival (OS) (P<0.001) and progression-free survival (PFS) times (P= 0.003, P<0.001) In multivariate analysis, PLR was a significant prognostic factor for OS (P<0.001) and PFS (P=0.003) time, whereas PLT was not a risk factor for PFS or OS time. According to the results of Cox regression analysis, a novel prognostic scoring system was created that combined PLR and β2-microglobulin level with International Prognostic Index value or age-adjusted International Prognostic Index value and the patients were divided into three groups: i) Low-risk patients with a PLR <170, International Prognostic Index (IPI) <2 scores or age-adjusted International Prognostic Index (aaIPI)= 0 and normal β2m; ii) high-risk patients with a PLR ≥170, IPI ≥4 or aaIPI=3 and high level of β2m; and iii) intermediate-risk patients. The novel score predicted 5-year OS rates of 86.4, 54.1 and 21.1% in the low-, intermediate-and high-risk groups, respectively (P<0.001). This novel prognostic scoring system may aid the evaluation of patient prognosis and guide treatment.

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Mesenchymal stromal cells are proven to be likely induce the angiogenic response in multiple myeloma and thus represent an enticing target for antiangiogenesis therapies for multiple myeloma. Substantial evidence indicates that angiogenesis in multiple myeloma is complex and involves direct production of angiogenic cytokines by abnormal plasma cells and these B-cell neoplasia generated pathophysiology change within the microenvironment. In this study, we demonstrated that mesenchymal stromal cells cultured with U266/Lp-1 under hypoxic conditions resulted in an increased α-smooth muscle actin expression and high productive levels of both hypoxia-inducible factor-2α and integrin-linked kinase proteins. Moreover, inhibition of hypoxia-inducible factor-2α by Small interfering RNA (siRNA) in mesenchymal stromal cells decreased the protein levels of both α-smooth muscle actin and integrin-linked kinase after mesenchymal stromal cells cultured with U266 under hypoxic conditions. We further demonstrated that transfection of integrin-linked kinase-siRNA reduced the protein level of α-smooth muscle actin and attenuated angiogenesis in vitro by decreasing the attachment of Q-dot labeled cells and secretion of angiogenic factors. In conclusion, our research showed that mesenchymal stromal cells cultured with myeloma cells under hypoxia participated in the angiogenesis of multiple myeloma, which is regulated by the hypoxia-inducible factor-2α-integrin-linked kinase pathway. Thus, targeting integrin-linked kinase may represent an effective strategy to block hypoxia-inducible factor-2α-induced angiogenesis in the treatment of multiple myeloma.