Browsing by Subject "Multiple myeloma"

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    CircKCNQ5 controls proliferation, migration, invasion, apoptosis, and glycolysis of multiple myeloma cells by modulating miR-335-5p/BRD4 axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Li, Yan; Wang, Liang; Zhang, Nan; Xu, Yan
    Background. Circular RNAs (circRNAs) are key players in tumorigenesis progression. However, the role and molecular mechanisms of circKCNQ5 in multiple myeloma (MM) progression remain unclear. Methods. The quantitative real-time polymerase chain reaction was used for examining circKCNQ5, miR-335-5p, and Bromodomain-containing protein 4 (BRD4) levels. The proliferation ability of MM cells was determined by Cell Counting Kit-8 and colonyforming assays. The migration and invasion were analyzed by transwell assay. Flow cytometry was used to assess cell apoptosis. The lactate production, glucose consumption, and ATP/ADP ratios were determined by commercialized kits. The protein levels were quantified by western blot analysis. The interactions between circKCNQ5 and miR-335-5p, along with miR-335-5p and BRD4 were analyzed by dual-luciferase reporter and RNA immunoprecipitation assays. Results. The overexpression of circKCNQ5 was confirmed in MM tissues and cells. Importantly, knockdown of circKCNQ5 suppressed proliferation, migration, invasion, and glycolysis while it increased apoptosis of MM cells in vitro. Interestingly, the downregulation of miR-335-5p was able to rescue the circKCNQ5 inhibition-induced effects on MM cells. MiR-335-5p interacted with circKCNQ5, and was able to target BRD4 in MM cells. MiR-335-5p upregulation inhibited malignant phenotypes of MM cells depending on BRD4. Conclusion. CircKCNQ5 was found to stimulate MM progression through competitively sponging to miR-335-5p.
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    Expression of eight genes of nuclear factor-kappa B pathway in multiple myeloma using bone marrow aspirates obtained at diagnosis
    (Murcia : F. Hernández, 2009) Sampaio Almeida, Manuella S.; Vettore, André L.; Yamamoto, M.; Chauffaille, Maria de Lourdes L.F.; Zago, Marco Antônio; Colleoni, Gisele W. B.
    Purpose: To evaluate the expression of NF- κB pathway genes in total bone marrow samples obtained from MM at diagnosis using real-time quantitative PCR and to evaluate its possible correlation with disease clinical features and survival. Material and methods: Expression of eight genes related to NF-κB pathway (NFKB1, IKB, RANK, RANKL, OPG, IL6, VCAM1 and ICAM1) were studied in 53 bone marrow samples from newly diagnosed MM patients and in seven normal controls, using the Taqman system. Genes were considered overexpressed when tumor expression level was at least four times higher than that observed in normal samples. Results: The percentages of overexpression of the eight genes were: NFKB1 0%, IKB 22.6%, RANK 15.1%, RANKL 31.3%, OPG 7.5%, IL6 39.6%, VCAM1 10% and ICAM1 26%. We found association between IL6 expression level and International Staging System (ISS) (p=0.01), meaning that MM patients with high ISS scores have more chance of overexpression of IL6. The mean value of ICAM1 relative expression was also associated with the ISS score (p=0.02). Regarding OS, cases with IL6 overexpression present worse evolution than cases with IL6 normal expression (p=0.04). Conclusion: We demonstrated that total bone marrow aspirates can be used as a source of material for gene expression studies in MM. In this context, we confirmed that IL6 overexpression was significantly associated with worse survival and we described that it is associated with high ISS scores. Also, ICAM1 was overexpressed in 26% of cases and its level was associated with ISS scores.
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    Increasing Therapy Related Myeloid Neoplasms in Multiple Myeloma
    (Wiley, 2018-11-13) Fernández-Caballero, M; Salmerón, D; Chen-Liang, TH; Hurtado, AM; García Malo, MD; Ortuño, FJ; Roldán, V; Vicente, V; Jerez, A; De Arriba, F; Chirlaque López, María Dolores; Ciencias Sociosanitarias
    Background: Despite the longer survival achieved in multiple myeloma (MM) patients due to new therapy strategies, a concern is emerging regarding an increased risk of secondary primary malignancies (SPMs) and how to characterize those patients at risk. We performed a retrospective study covering a 28‐year follow‐ up period (1991‐2018) in a tertiary single institution. Material and Methods: Data of 403 MM patients were recorded and compared with the epidemiologic register of the population area covered by our centre, calculating the standardize incidence ratio (SIR) for the different types of SPMs diagnosed in the MM cohort. Fine and Gray regression models were used to identify risk factors for SPMs. Results: Out of the 403 MM patients, 23 (5.7%) developed SPMs: 13 therapyrelated myeloid (TRM) malignancies (10 of them (77%) myelodysplastic syndrome (MDS), 1 acute lymphoid leukaemia and 9 solid neoplasms. In the MM cohort, the relative risk of MDS was significantly higher than in the general population. Survival of patients with TRM malignancies was poor with a median of 4 months from the diagnosis, and most of them showed complex karyotype. Within the MM subset, multivariable analysis showed a higher risk of TRM malignancies in patients that previously received prolonged treatment with lenalidomide (>18 months). Conclusions: Though the improvement in MM outcome during the last decades is an unprecedented achievement, it has been accompanied by the rise in TRM malignancies with complex cytogenetic profile and poor prognosis that are in the need of an improved biologic and therapeutic approach.
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    Plasma cell quantification in bone marrow by computer-assisted image analysis
    (Murcia : F. Hernández, 2006) Went, P.; Mayer, S.; Oberholzer, M.; Dirnhofer, S.
    Background: Minor and major criteria for the diagnosis of multiple meloma according to the definition of the WHO classification include different categories of the bone marrow plasma cell count: a shift from the 10- 30% group to the >30% group equals a shift from a minor to a major criterium, while the <10% group does not contribute to the diagnosis. Plasma cell fraction in the bone marrow is therefore critical for the classification and optimal clinical management of patients with plasma cell dyscrasias. The aim of this study was (i) to establish a digital image analysis system able to quantify bone marrow plasma cells and (ii) to evaluate two quantification techniques in bone marrow trephines i.e. computer-assisted digital image analysis and conventional light-microscopic evaluation. The results were compared regarding inter-observer variation of the obtained results. Material and methods: Eighty-seven patients, 28 with multiple myeloma, 29 with monoclonal gammopathy of undetermined significance, and 30 with reactive plasmocytosis were included in the study. Plasma cells in H&E- and CD138-stained slides were quantified by two investigators using light-microscopic estimation and computer-assisted digital analysis. The sets of results were correlated with rank correlation coefficients. Patients were categorized according to WHO criteria addressing the plasma cell content of the bone marrow (group 1: 0-10%, group 2: 11-30%, group 3: >30%), and the results compared by kappa statistics. Results: The degree of agreement in CD138-stained slides was higher for results obtained using the computer-assisted image analysis system compared to light microscopic evaluation (corr.coeff.=0.782), as was seen in the intra- (corr.coeff.=0.960) and inter-individual results correlations (corr.coeff.=0.899). Inter-observer agreement for categorized results (SM/PW: kappa 0.833) was in a high range. Conclusions: Computer-assisted image analysis demonstrated a higher reproducibility of bone marrow plasma cell quantification. This might be of critical importance for diagnosis, clinical management and prognostics when plasma cell numbers are low, which makes exact quantifications difficult.
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    The role of the bone marrow microenvironment in multiple myeloma
    (Murcia : F. Hernández, 2005) De Raeve, H.; Vanderkerken, K.
    Multiple myeloma (MM) is a malignant disease that results from an excess of monotypic plasma cells in the bone marrow (BM). This malignancy is characterised by complex karyotypic aberrancies. In 60% of all MM there are recurrent primary translocations involving the heavy chain gene locus. The MM cells strongly interact with the BM microenvironment, which is composed of endothelial cells, stromal cells, osteoclasts, osteoblasts, immune cells, fat cells and the extracellular matrix. This interaction is responsible for the specific homing in the BM, the proliferation and survival of the MM cells, the resistance of MM cells to chemotherapy, the development of osteolysis, immunodeficiency and anaemia. New therapeutic agents target both the MM, as well as the interaction MM cell – BM microenviroment.