25-Hydroxy vitamin D deficiency predicts inferior prognosis in mantle cell lymphoma.

INTRODUCTION: Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin lymphoma (NHL), and the purpose of this study was to evaluate the prognostic value of 25-hydroxy vitamin D [25-(OH)D] deficiency among patients with MCL. MATERIALS AND METHODS: Seventy MCL patients with serum 25-(OH)D were enrolled in this study. 25-(OH)D deficiency was defined as a 25-(OH)D level lower than 50 nmol/L, according to International standard of 25-(OH)D classification. The univariate and multivariate Cox regression analyses were used to define the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curves and the areas under the curve (AUC) were calculated to evaluate the accuracy of combined MIPI-c with 25-(OH)D deficiency. RESULTS: The results showed that 40 patients had 25-OH vitamin D deficiency, with a median follow-up of 25.5 months (range 3.4-65.7 months). Univariate Cox regression analysis showed that 25-(OH)D deficiency group demonstrated unfavorable PFS (P = 0.003) and OS (P = 0.006). Multivariate Cox regression analysis revealed that 25-(OH)D deficiency was an independent prognosis factor for PFS [hazard ratio (HR) 3.713; 95% confidence interval (CI) 1.822-7.565; P < 0.001], and OS (HR 8.305; 95% CI 2.060-33.481; P = 0.003). 25-(OH)D deficiency combined with MIPI-c showed an improved prognostic capacity. CONCLUSION: In summary, 25-(OH)D deficiency was a promising prognostic predictor for MCL.

EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-Barr Virus Associated Chronic Lymphocytic Leukemia.

PURPOSE: The purpose of this study was to investigate the prognostic impact of Epstein-Barr virus (EBV)-microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene. MATERIALS AND METHODS: Quantitative reverse transcription-polymerase chain reaction and western blotting were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. RESULTS: p53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p < 0.001) which was also an independent prognostic marker for overall survival (p=0.028; hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLL patients after adjusted with International Prognostic Index for patients with CLL. We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3'- untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1- 1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines. CONCLUSION: This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.