EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-BarrVirus Associated Chronic Lymphocytic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

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 wellas role of EBV-miR-BHRF1-1 in p53 gene. @*Materials and Methods@#Quantitative reverse transcription–polymerase chain reaction and western blotting wereused 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 CLLpatients after adjusted with International Prognostic Index for patients with CLL. We identifiedEBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressedluciferase reporter activity by specific interaction with the seed region within the p53 3-untranslated region. Discordance of p53 messenger RNA and protein expression wasassociated 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 apoptosisand decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferationin cell lines. @*Conclusion@#This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our resultssupport the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLLwith p53 gene aberration.

Albumin-to-Fibrinogen Ratio as an Independent Prognostic Parameter in Untreated Chronic Lymphocytic Leukemia: A Retrospective Study of 191 Cases / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Chronic lymphocytic leukemia (CLL) is one of the most frequent type of B-cell chronic lymphoproliferative disorders and chronic inflammation takes part in the development of CLL. However, there has been no valid immune biomarker to predict the prognosis of untreated CLL patients. MATERIALS AND METHODS: In this retrospective study, we analyzed the clinical correlations and prognostic value of albumin-to-fibrinogen ratio (AFR) detected at diagnosis in 191 CLL patients. RESULTS: The cut-off value of AFR was 9.7 calculated by X-tile. Patients who were more than 65 years old were often accompanied by low level of AFR (p < 0.001). Survival analysis showed that patients with low level of AFR had shorter overall survival (OS) than patients with high level of AFR (p < 0.001). Multivariate analysis illustrated that AFR had a negative impact on OS (p=0.003) and was independent of parameters involved in CLL international prognostic index and other prognostic markers such as CD38 and ZAP-70. CONCLUSION: These data provide a comprehensive view of AFR and shows that AFR at diagnosis is an adverse prognostic factor in untreated CLL patients.

Presence of serum antinuclear antibodies correlating unfavorable overall survival in patients with chronic lymphocytic leukemia / 中华医学杂志(英文版)

BACKGROUND@#Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL.@*METHODS@#This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS). Receiver operator characteristic curves and area under the curve (AUC) were utilized to assess the predictive accuracy of ANAs together with other independent factors for OS.@*RESULTS@#The incidence of ANAs abnormality at diagnosis was 13.9%. ANAs positivity and TP53 disruption were independent prognostic indicators for OS. The AUC of positive ANAs together with TP53 disruption was 0.766 (95% confidence interval [CI]: 0.697-0.826), which was significantly larger than that of either TP53 disruption (AUC: 0.706, 95% CI: 0.634-0.772, P = 0.034) or positive ANAs (AUC: 0.595, 95% CI: 0.520-0.668, P < 0.001) in OS prediction. Besides, serum positive ANAs as one additional parameter to CLL-international prognostic index (IPI) obtained superior AUCs in predicting CLL OS than CLL-IPI alone.@*CONCLUSION@#This study identified ANAs as an independent prognostic factor for CLL, and further investigations are needed to validate this finding.

Survival analysis of 118 chronic lymphocytic leukemia patients with abnormal TP53 gene in the era of traditional immunochemotherapy / 中华血液学杂志

Objective: To analyze the survival and first-line immune-chemotherapy (CIT) of chronic lymphocytic leukemia (CLL) with abnormal TP53 gene in the era of traditional CIT. Methods: The clinical data of 118 CLL patients diagnosed from January 2003 to August 2017 were collected. Survival was analyzed according to indicators including sex, age, Binet risk stratification, B symptoms, β(2)-microglobulin (β(2)-MG) , immunoglobulin heavy chain variable region gene (IGHV) mutation status, chromosome karyotype and TP53 gene deletion/mutation. The efficacy of first-line CIT of 101 CLL patients was further analyzed. Results: Among 118 patients, median progression-free survival (PFS) was 12 (95%CI 10.148-13.852) months and median overall survival (OS) was 53 (95%CI 41.822-64.178) months, only 30.5% patients survived over 5 years. Low β(2)-MG<3.5 mg/L indicated longer PFS (P=0.027) , female and Binet A patients had longer OS (P=0.011 and 0.013, respectively) . Of 118 patients, 17 (14.4%) didn't receive any therapy until follow-up time or the dead time. Among the 101 patients who received ≥1 CIT, median time to first treatment (TTFT) was 1 (0-62) months, patients in Binet A had longer TTFT (P<0.001) compared to the patients in Binet B/C. According to statistical needs, we divided those first-line CIT into four groups: there were 30 cases (29.7%) in mild chemotherapy group (mainly treated with nitrogen mustard phenylbutyrate or rituximab alone) , 32 cases (31.7%) in the fludarabine-containing group, 23 cases (22.8%) in high-dose methyprednisolone (HDMP) containing group and 16 cases (15.8%) in the other chemotherapy group. The first regimen contained HDMP can bring longer PFS (P<0.001) , however the OS between four groups had no statistical differences. Conclusion: CLL patients with abnormal TP53 gene had poor response to immunotherapy, rapid clinical progressing, first-line immunotherapy containing HDMP can prolong PFS and will create an opportunity for patients to participate in clinical trials of novel drugs.

The prognostic significance of peripheral lymphocyte/monocyte ratio and PET-2 evaluation in adult Hodgkin's lymphoma / 中华血液学杂志

Objective: To evaluate the prognostic value of lymphocyte to monocyte ratio (LMR) and PET scan performed after first two cycles of chemotherapy (PET-2) in Hodgkin's lymphoma (HL) . Methods: The clinical data of 133 patients with HL diagnosed from January 2007 to March 2016 at the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The X-tile software was used to calculate the optimal cut-off value of LMR. Kaplan-Meier method and Cox regression were used for survival analysis. Results: The median age of 133 HL patients was 33 (18-84) years, and the male to female ratio was 1.9∶1. The optimal cut-off value of LMR was 2.5, and progression free survival (PFS) (P<0.001) and overall survival (OS) (P<0.001) were significantly lower in the LMR<2.5 group than that of LMR≥2.5. Multivariate survival analysis showed that LMR<2.5 was an independent predictor of PFS (P=0.002, HR=2.35, 95%CI 1.36-4.07) and OS (P=0.002, HR=10.36, 95%CI 2.35-45.66) in HL patients. The analysis of PET-2 from 56 HL patients showed that PET-2 positive patients had significantly poorer PFS (P=0.022) . After grouping LMR combined with PET-2, significant differences were found in PFS and OS between the three groups (P values were 0.009 and 0.012) . Conclusion: LMR<2.5 is an independent prognostic factor for patients with HL. PET-2 combined with LMR may have better prognostic value.

Prognostic value of lymphocyte-to-monocyte ratio in angioimmunoblastic T cell lymphoma / 中华血液学杂志

Objective: To evaluate the prognostic value of lymphocyte-to-monocyte ratio (LMR) in angioimmunoblastic T cell lymphoma (AITL). Methods: Data of 64 patients diagnosed as AITL at the First Affiliated Hospital of Nanjing Medical University between June 2009 and July 2017, were analyzed retrospectively. Receiver Operator Characteristic (ROC) curve was used to calculate the cutoff value of LMR to divide this cohort of patients into high and low LMR groups. Characteristics between groups were compared by Pearson Chi-square or Fisher exact tests. Kaplan-Meier method and Cox regression were performed to probe prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Results: A total of 64 cases [39 cases male and 25 ones female with the median age of 63 (29-89) years old] were enrolled. The cutoff value of LMR was 3.07. Patients with low LMR showed inferior PFS (9 months vs 13 months, P=0.044) and OS (16 months vs not reached, P=0.014), respectively than those without low LMR during a median follow-up of 33 months (5 to 103 months). Multivariate analysis showed that low LMR was an independent prognostic factor associated with poor outcomes (HR=0.48, 95% CI 0.26-0.92 for PFS, P=0.027; HR=0.38, 95% CI 0.18-0.82 for OS, P=0.013, respectively). Subgroup analysis showed that patients with low LMR and under the situation of high score of Prognostic Index for peripheral T-cell lymphoma, Unspecified (PIT) (2-4) had shorter PFS and OS (P=0.013 and P=0.031, respectively). But in low score of PIT (0-1) group, low LMR seemed to play almost no effects on PFS and OS (P=0.949 and P=0.238, respectively). Conclusions: The disease risk status of patients could be initially assessed according to PIT score and LMR level. Low LMR was demonstrated to be able to predict poor outcome in AITL.