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Background Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. Objective We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. Results We studied 349 older patients with newly diagnosed MM (age range, 65–86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA ‘fit’ group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1–38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). Conclusions Our study justifies the need for a CGA in older patients with newly diagnosed MM.

The aim of the study was to investigate whether microvessel density (MVD) could be associated with skeletal extramedullary disease relapse (skeletal-EMDR) in patients with multiple myeloma (MM) who have skeletal-EMD at diagnosis. Seventy-nine newly diagnosed MM patients who have skeletal-EMD were retrospectively enrolled in this study. The 4-year cumulative incidence of skeletal-EMDR was 35.0%±8.3%. The 4-year probability of overall survival (OS) was 54.0%±7.6%. Multivariate analysis showed that skeletal-EMDR (HR = 4.144; 95% CI: 1.608–10.685; P = 0.003) was independently associated with inferior OS for the MM patients who have skeletal-EMD at diagnosis. The factors associated with skeletal-EMDR were MVD (HR = 3.990, 95%CI:1.136-14.018; P = 0.031), white blood cell (WBC) (HR = 0.262, 95% CI:0.090-0.769; P = 0.015), and the EMD sites involved at onset (HR = 0.263, 95% CI: 0.074-0.937; P = 0.039). The MVD in patients with thoracic and lumbar vertebrae as the involved sites at diagnosis was significantly lower than those with other sites involved (41.59 ± 14.39 vs. 60.82 ± 35.14, P=0.001). Our data suggest that increased MVD could be used to predict skeletal-EMDR, which is associated with inferior survival in patients with MM who have skeletal-EMD at diagnosis.

MicroRNA (miR)-19a, as an oncomiR, has been studied in several types of cancer; however, its role in the development and progression of multiple myeloma (MM) remains unclear. The present study used a bioinformatics approach to investigate the involvement of miR-19a in MM. miR-19a targets were predicted using target prediction programs, followed by screening for differentially expressed genes in MM. The function of these genes was then annotated using gene ontology term enrichment, signaling pathway enrichment and protein-protein interaction (PPI) analysis. In addition, natural language processing (NLP) was performed to identify genes associated with MM. A total of 715 putative targets of miR-19a were identified in the present study, of which 40 were experimentally validated. A total of 121 genes were identified to be differentially expressed in MM, including 80 upregulated genes and 41 downregulated genes. Among the differentially expressed genes, ras homolog family member B, clathrin heavy chain, prosaposin and protein phosphatase 6 regulatory subunit 2 were predicted target genes of miR-19a. The results of NLP revealed that 2 of the differentially expressed genes, Y-box binding protein 1 and TP53 regulated inhibitor of apoptosis 1, were reported to be associated with MM. In addition, 41 target genes of miR-19a were identified to be associated with the development and progression of MM. These results may aid in understanding the molecular mechanisms of miR-19a in the development and progression of MM. In addition, the results of the present study indicate that targets genes of miR-19a are potential candidate biomarkers for MM.

The goal of the study was to investigate the expression of interleukin-17 (IL-17) and IL-17 receptor (IL-17R) in patients with myeloma bone diseases (MBD) and skeletal extramedullary disease (skeletal EMD). The levels of IL-17 were determined using ELISA. The expression of IL-17R on vascular endothelial cells of bone marrow (BM) and masses of skeletal EMD was detected using immunohistochemistry. The results showed an elevated IL-17 level in BM of BMD and skeletal EMD patients. The microvessel density (MVD) was significantly increased in the masses of skeletal EMD. IL-17R was almost exclusively expressed by endothelial cells, not by myeloma cells in the masses of skeletal EMD patients. We concluded that EMD masses showed increased angiogenesis mediated by IL-17 pathway and in part this may help in myeloma cell-growth under these conditions.

The goal of the study was to investigate the levels of interleukin-27 (IL-27) and IL-17 in bone marrow (BM) and peripheral blood (PB) of multiple myeloma (MM). The levels of IL-27 and IL-17 were determined in MM patients and controls using ELISA. The results showed a decreased IL-27 and elevated IL-17 level in MM patients and a negative association of IL-27 with IL-17. The ratio of IL-27:IL-17 in BM of newly diagnosed MM was significantly decreased and correlated with the progression of disease. Multivariate analysis showed that a higher ratio of IL-27:IL-17 in BM was associated with a superior progression-free survival (HR=0.160; 95% CI: 0.058-0.443; p

Norcantharidin (NCTD), the demethylated analog of the Chinese medicine cantharidin, exhibits anti-myeloma activity by inactivating nuclear factor-κB (NF-κB), which is implicated in multiple myeloma (MM) cell survival and resistance to bortezomib (BTZ). We investigated whether NCTD could potentiate the anti-tumor activity of BTZ in MM. NCTD inhibited the proliferation of MM cells and potentiated the anti-myeloma effects of BTZ by down-regulating IKKα and p-IκBα, which induced the accumulation of IκBα and inhibited the constitutive activation of NF-κB. This effect was correlated with the suppression of NF-κB-regulated gene products. Furthermore, a chemotherapy-potentiating effect of NCTD on BTZ was also observed in vivo. Our study demonstrated that NCTD and BTZ exhibit significant therapeutic effects on MM through the NF-κB signal pathway in vitro and in vivo. Future studies will investigate the combined effects of NCTD and BTZ in patients with MM.

To explore the synergetic effect of norcantharidin (NCTD) and adriamycin (ADR) on the proliferation and apoptosis of multiple myeloma (MM) cells.Human MM cell line U266 cells were treated with NCTD alone (10 µmol/L) or in combination with ADR (0.25 µmol/L). MTT and Annexin V/PI staining were used to determine cell viability and apoptosis. The protein expression of nuclear factor-κB P65 (NF-κB P65), phosphorylated NF-κB p65 (p-NF-κB p65), NF-κB P65 inhibitor IκBα, phosphorylated IκBα (p-IκBα), survivin, Bcl-2 and Bax were determined by Western blot. Immunohistochemistry was used to determine the expression of vascular endothelial growth factor (VEGF).(1) NCTD potentiated the cytotoxicity and pro-apoptotic effects induced by ADR. The combination of NCTD and ADR had synergistic anti-proliferation effect. (2) Combination of ADR and NCTD downregulated the expression of nuclear NF-κB P65 and cytoplasm p-IκBα induced by ADR. The expression of nuclear NF-κB P65 and cytoplasm p-IκBα decreased from 2.08 ± 0.29 and 0.39 ± 0.07 to 0.48 ± 0.08 and 0.02 ± 0.01 respectively, while the expression of the cytoplasm NF-κB P65 and IκBα were unchanged in the ADR alone group and the combined group. (3) The expression of survivin and bcl-2 decreased from 0.31 ± 0.05 and 0.23 ± 0.05 to 0.03 ± 0.02 and 0.05 ± 0.02, while the expression of Bax increased from 0.46 ± 0.06 to 0.62 ± 0.08 respectively in ADR alone group and combined group. (4) The positive rate of VEGF in ADR group and combination group were (44.6 ± 4.4)% and (27.0 ± 2.1)% respectively, indicating that NCTD could potentiate the inhibition effect on VEGF induced by ADR.The results suggest that NCTD can potentialize the chemosensitivity of multiple myeloma cells to ADR through regulating NF-κB/IκBα signaling pathway and NF-κB-regulated gene products including survivin, Bcl-2, Bax and VEGF.