Expression of NEAT1 can be used as a predictor for Dex resistance in multiple myeloma patients.

OBJECTIVE: Multiple myeloma is a heterogeneous disorder and the intratumor genetic heterogeneity contributes to emergency of drug resistance. Dexamethasone has been used clinically for decades for MM. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of Dex resistance. LncRNA NEAT1 plays a oncogenic role and participates in drug resistance in many solid tumors. Therefore, we investigated a potential usefulness of this molecular as a biomarker for diagnosis of MM and possible correlations of NEAT1 expression with drug resistance and prognosis. METHODS: Bone marrow and peripheral blood mononuclear cells samples were collected from 60 newly diagnosed MM patients. The expression of NEAT1expression level were detected by quantitative real-time PCR analyses. The relationship about the expression levels of lncRNA with other clinical and cytogenetic features was analyzed. In addition, we measured to analysis the correlation between the expression of NEAT1 and Dex resistance in MM patients. RESULTS: It was found that the expression of NEAT1 is significantly higher in multiple myeloma patients compared to controls and does not change with other clinical features and cytogenetic features. We further discovered that overexpression of NEAT1 was associated with Dex resistance and a poor prognosis in MM patients. CONCLUSION: LncRNA NEAT1 has a significant value that might act as a promoting factor in the development of MM and may be severed as a diagnostic factor in MM. NEAT1 invovled in Dex resistance, which provide a new interpretation during the chemotherapy for MM.

Coexistence of Pure Red Cell Aplasia and Autoimmune Haemolytic Anaemia Associated with Thymoma.

Thymoma is an uncommon neoplasia derived from the epithelial cells of the thymus, which leads to immune dysregulation and is associated with a series of autoimmune diseases. However, the concurrence of these disease entities is rare, and the exact mechanisms of these diseases are still unclear. We have admitted several cases who were diagnosed with thymoma, autoimmune haemolytic anaemia, and pure red cell aplasia. These cases were the first to report the concurrence of these three disorders. After thymectomy, anaemia improved, haemolytic cells decreased, and haemoglobin was normalized.

Orai1 and Stim1 Mediate the Majority of Store-Operated Calcium Entry in Multiple Myeloma and Have Strong Implications for Adverse Prognosis.

BACKGROUND/AIMS: Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies. Despite the development and application of novel agents, MM still undergoes an aggressive and incurable course in the vast majority of patients. Ca2+ is one of the critical regulators of cell migration. Ca2+ influx is essential for the migration of various types of cells including tumor cells. However, the role of store-operated calcium entry (SOC) channels, the only Ca2+ channels of non-excitable cells, has not yet been reported in MM cell survival. METHODS: We evaluated the expression of Stim1 and Orai1 (two key regulators of SOC) in MM tissues and cell lines by immunohistochemical assay, quantitative real-time PCR assay and western blot. MM cell lines were pretreated with pharmacological blockers and siRNAs, and then MM cell proliferation, cell cycle arrest, and apoptosis were examined by FACS (flow cytometry) assay, and Annexin V-FITC/PI staining. The correlation between the expression of Stim1 (or Orai1) level and outcome in MM were assessed by using Progress Free Survival (PFS). RESULTS: Stim1 and Orai1 were both abundantly expressed in MM tissue and MM cell lines. Inhibition of SOCE reduced MM cell viability, and induced cell cycle arrest and apoptosis. Stim1 or Orai1 silencing also reduced cell viability, caused cell apoptosis and cell cycle arrest in MM cell lines. Over-expression of Stim1/Orai1 in MM patients was closely associated with the clinical outcome of MM. CONCLUSION: The Stim1/Orai1-mediated signaling participates in the pathogenesis of MM, which represents an attractive target for future therapeutic intervention.

Expression of Peripheral Blood miRNA-720 and miRNA-1246 Can Be Used as a Predictor for Outcome in Multiple Myeloma Patients.

OBJECTIVE: Multiple myeloma (MM) is a heterogeneous disorder, encompassing several related entities that share the common characteristic of being composed of monoclonal plasma cells (PCs). MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of many target messenger RNAs involved in normal cell functions. Two serum microRNAs, miRNA-720 and miRNA-1246, were found to have potential as diagnostic biomarkers in myeloma. Therefore, we investigated a possible correlation of peripheral blood (PB) miRNA expression with diagnosis and prognosis. METHODS: We measured the expression of PB miRNA-720 and miRNA-1246 in 60 newly diagnosed MM patients by quantitative real-time PCR analyses. And analysed the relationship about the expression levels of miRNAs with other clinical features. RESULTS: The expression levels of PB miRNAs are significantly higher in myeloma patients compared to controls and do not change with age, gender, disease stage, hemoglobin, bone marrow PC percentage, ß2 microglobulin, serum albumin, calcium serum, serum creatinine, and myeloma protein, and independent of the deletion of chromosome 13, suggesting that the expression levels of PB miRNA-720 and miRNA-1246 can be used as a diagnostic test for myeloma. We first discovered that increased expression of PB miRNA-720 and miRNA-1246 were associated with shorter progression-free survival, indicating poor prognosis. CONCLUSION: Our study demonstrated that PB miRNA-720 and miRNA-1246 might act as a promoting factor in the development of MM and could be a diagnostic factor, therapeutic effect evaluator, and prognostic indicator in the prognosis of MM. The miRNAs have a significant value of appreciation of individual patients' behavior during the chemotherapy and evaluation the therapeutic strategies.

Expression of the significance of silent information regulator type-1 in Angioimmunoblastic T-cell lymphoma is greater association with tumorigenesis and has strong implications for adverse prognosis.

Silent information regulator type-1 (SIRT1) is the best-studied member of the Sirtuin (Sir2) family of nicotinamide dinucleotide (NAD)-dependent class III histone deacetylases (HDACs). Rrecently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma, but has not yet been explored in Angioimmunoblastic T-cell lymphoma (AITL). Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in AITL. Immunohistochemical expression of SIRT1, p53 were evaluated by using a 2 mm core from 45 AITL patients. Positive expression of SIRT1 was seen in 71.11% (32 of 45) of patients and p53 expression were seen in 53.33% (24 of 45). SIRT1 and p53 expression were significantly associated with shorter PFS by univariate analysis (P=0.009 and P < 0.001, respectively), multivariate analysis also shows that SIRT1 expression relate to worse prognosis. We also suggest inferior survival in AITL with the combined expression of SIRT1 and clinical characteristics of high IPI scores, high clinical stage, increased serum LDH, decreased HGB and increased γ-Globulin. In conclusion, our results indicate that SIRT1 is strongly expressed in AITL and it act as a clinically significant prognostic indicator for AITL patients, may also serve as a therapeutic target in AITL.