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Xiao-Yu Su,1 Qian Zhao,1 Jin-Ming Ke,2 De-Hong Wu,1 Xin Zhu,1 Jiang Lin,1 Zhao-Qun Deng1 1Laboratory Center, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2Faculty of Forestry, Zhejiang A&F University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Zhao-Qun DengLaboratory Center, The Affiliated People’s Hospital of Jiangsu University, 8 Dianli Road, Zhenjiang, Jiangsu 212002, People’s Republic of ChinaFax +86 51185234387Email zqdeng2002@163.comPurpose: Our research aimed to investigate the expression level of circ_ 0002232, which is transcribed from PTEN, and find out the association of circ_0002232/miR-92a-3p/PTEN network in acute myeloid leukemia (AML).Methods: Circ_0002232 expression in 115 AML patients and 48 controls was detected by using real-time quantitative PCR. The diagnostic value of circ_0002232 expression was evaluated by receiver operating characteristic curve. Kaplan–Meier curves were used to analyse the impact of circ_0002232 for overall survival. Associated network of circ_0002232 was predicted by using interaction prediction websites.Results: Compared with controls, circ_0002232 was notably low-expressed in AML (P< 0.001). According to the result of receiver operating characteristic curve, circ_0002232 expression could distinguish AML patients from controls (P< 0.001). There were significant differences in patients’ age (P=0.004), FAB classifications (P=0.036), white blood cell count (P=0.041) and platelet count (P=0.021) between low-expressed circ_0002232 group and high-expressed circ_0002232 group. Moreover, there was a positive correlation between circ_0002232 expression and patients’ age (Pearson r=0.256, P=0.0057). Interestingly, we found that patients in low-expressed circ_0002232 group had better overall survival both in whole AML (P=0.030) and non-APL AML (P=0.014). Remarkably, the expression of circ_0002232 was positively correlated with PTEN (Spearman r=0.678, P< 0.001). Furthermore, there was a negative correlation in AML between circ_0002232 and miR-92a-3p (Spearman r=− 0.301, P=0.016), miR-92a-3p and PTEN (Spearman r=− 0.324, P=0.034). Interaction prediction websites revealed that circ_0002232 might affect the expression of PTEN and the process of AML through sponging miR-92a-3p.Conclusion: Circ_0002232, one of the circRNAs transcribed from PTEN, was remarkably down-regulated in AML and could act as a promising biomarker for the diagnosis of AML. In addition, there might be a potential association network of circ_0002232/miR-92a-3p/PTEN in AML.Keywords: circular RNAs, circ_0002232, miR-92a-3p, PTEN, acute myeloid leukemia

Xi-xi Li,1,2,* Jing-dong Zhou,1,3,4,* Xiang-mei Wen,3,5,* Ting-juan Zhang,1,3,4 De-hong Wu,6 Zhao-qun Deng,3,5 Zhi-hui Zhang,1,3,4 Xin-yue Lian,1,3,4 Pin-fang He,1,3,4 Xin-yu Yao,7 Jiang Lin,3,5 Jun Qian1,3,4*These authors contributed equally to this work1Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2Department of Hematology, The Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Zhenjiang Clinical Research Center of Hematology, Zhenjiang, Jiangsu, People’s Republic of China; 4The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Zhenjiang, Jiangsu, People’s Republic of China; 5Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 6Department of Hematology, The Third People’s Hospital of KunShan City, 215300 Kunshan, People’s Republic of China; 7School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of ChinaBackground:Altered expression of the BCL-2 family member MCL-1 has been linked to the progression and outcome of various malignancies. Recently, MCL-1 inhibitor S63845 was reported to kill MCL-1-dependent cancer cells and has potential value in clinical application.Purpose: Herein, we reported MCL-1 expression pattern in Chinese de novo acute myeloid leukemia (AML) and its impact on prognosis and may provide theoretical basis for AML patients using MCL-1 inhibitor in clinics. Real-time quantitative PCR was carried out to detect the transcript of MCL-1 in AML patients.Results: MCL-1 expression was significantly up-regulated in AML compared with controls (P=0.042). We divided the patients into two groups (higher and lower expression of MCL-1) based on the median level. Among both non-acute promyelocytic leukemia (APL) and cytogenetically normal AML (CN-AML), patients with higher expression of MCL-1 correlated with lower complete remission (CR) rate (P=0.031 and 0.004, respectively) and shorter overall survival (OS) time (P=0.008 and 0.004, respectively) compared with those with lower expression of MCL-1. Meanwhile, Cox regression analyses revealed that overexpression of MCL-1 acted as an independent risk factor for OS in non-APL patients and CN-AML patients (P=0.011 and 0.045, respectively). In follow-up patients, MCL-1 expression level decreased after CR compared with newly diagnosis time (P=0.020) and increased after relapse (P=0.004).Conclusion: Our findings suggest that higher expression of MCL-1 predicts poor prognosis and can be used for disease monitoring.Keywords: MCL-1, expression, prognosis, recurrence, acute myeliod leukemia

Lan Yang,1,2,* Jing-Dong Zhou,2,3,* Ting-Juan Zhang,2,3 Ji-Chun Ma,1,2 Gao-Fei Xiao,1,2 Qin Chen,1,2 Zhao-Qun Deng,1,2 Jiang Lin,1,2 Jun Qian,2,3 Dong-Ming Yao1,2 1Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2The Key Laboratory of Precision Diagnosis and Treatment of Zhenjiang City, Zhenjiang, Jiangsu, People’s Republic of China; 3Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China *These authors contributed equally to this work Background and purpose: Abundant studies have shown that lncRNA PANDAR plays an oncogenic role in human solid tumors. Although abnormal expression of PANDAR has been well investigated in solid tumors, it was rarely studied in hematologic diseases. Hence, the aim of this study was to determine the PANDAR expression level and its clinical significance in patients with acute myeloid leukemia (AML).Materials and methods: For detecting the expression level of PANDAR in 119 AML patients and 26 controls, real-time quantitative PCR was used in this study. The prognostic values were evaluated by using Kaplan–Meier analysis, Cox regression analyses, and logistic regression analysis.Results: PANDAR was significantly overexpressed in AML and might be a promising biomarker which could distinguish AML from normal samples (P

Background: Dysregulation of miR-675 has been found in a variety of solid tumors. MiR-675 has been suggested as having both oncogenic and tumor suppression properties in cancer. However, there is no evidence whether miR-675 is involved in breast cancer. The objective of this study was to evaluate the expression status of miR-675 and its clinical relevance in breast cancer patients. Methods: The expression level of miR-675 was detected in 100 breast cancer patients and 38 cancer-free controls using real-time quantitative PCR. The clinicopathological characteristics of miR-675 in breast cancer were also investigated. All statistical analyses were performed using SPSS 20.0. Results: The study showed that miR-675 was significantly up-regulated in breast cancer patients compared with controls (P < 0.01). There was no significant difference in age, lymph nodes stage, ER status and PR status between patients with and without miR-675 over-expression (P > 0.05). The frequency of miR-675 over-expression was higher in the patients of histological grade I-II than in others (50% versus 9%, P = 0.011). The expression level of miR-675 had a high correlation with miR-24/93/98/378 in breast cancer patients. Conclusions: Taken together, our study demonstrated that miR-675 in formalin-fixed paraffin-embedded (FFPE) tissues might serve as a good source for biomarker discovery and breast cancer validation.

Background: Aberrant expression of miR-378 has been observed in various malignancies including acute myeloid leukemia (AML). However, the mechanism regulating of miR-378 expression remains unknown. This study was aimed to investigate miR-378 methylation and to explore its clinical significance in AML. Methods: Methylation status of miR-378 5’-flanking region was investigated by real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite-sequencing PCR (BSP). The expression of miR-378 was evaluated by real-time quantitative PCR (RQ-PCR). The correlation between expression of miR-378 and 5’-flanking region methylation was analyzed using 5-aza-2’-deoxycytidine (5-aza-dC) treatment. Results: miR-378 5’-flanking region was significantly hypomethylated in AML patients compared to controls (median 0.109 vs. 0.058) (P=0.048). miR-378 expression was correlated with miR-378 5’-flanking region in leukemic cell line treated with 5-aza-dC, but not in AML patients. The level of miR-378 hypomethylation significantly increased in M2 subtype compared to other subtypes. Moreover, patients with t(8;21) harbored the highest level of miR-378 hypomethylation. However, there was no significant difference in overall survival between patients with high and low miR-378 hypomethylation. The association of miR-378 expression with methylation was not observed in AML patients, but miR-378 expression in THP-1 line was increased while methylation status of miR-378 5-flanking region was decreased after 5-aza-dC treatment. Conclusions: Our findings suggest that miR-378 is reactivated by demethylation after 5-aza-dC treatment. 5’-flanking region of miR-378 is hypomethylated in AML especially in those with t(8;21).

Overexpression of MAPK/MAK/MRK overlapping kinase (MOK) has been found in various tumors. However, the mechanism underlying MOK upregulation remains unclear. A CpG island was identified in MOK promoter. In this study, we evaluated the expression and methylation status of MOK gene in acute myeloid leukemia (AML). Hypomethylation of MOK promoter was detected in 31.0% (45/145) of AML patients. The degree of MOK hypomethylation was significantly correlated with MOK expression in AML patients. MOK-hypomethylated patients had a trend towards lower WBCs. Receiver operating characteristic curve (ROC) analysis showed a good performance in distinguishing AML patients from controls with an area under the ROC curve (AUC) of 0.820 (P < 0.001). In summary, our results suggest MOK promoter hypomethylation is a common event and contributes to MOK overexpression in AML.

This study was designed to learn the expression status of miR-24 and its clinical relevance in patients with acute myeloid leukemia (AML). We detected the miR-24 expression levels using real-time quantitative PCR in 84 AML patients and investigated the clinical significance of miR-24 expression in AML. There was no difference in clinical parameters between cases with miR-24 high expression and with miR-24 low expression. The frequency of miR-24 high expression was higher in patients with t(8;21) than in others (82% (9/11) versus 44% (32/72), P=0.026). The levels of miR-24 expression had no correlation with the mutations of nine genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, N/K-RAS and C/EBPA). Meanwhile, among the group who obtained CR, the cases with miR-24 high expression had no difference in overall survival (OS) and relapse-free survival (RFS) than those with miR-24 low expression (P=0.612 and 0.665, respectively). These findings implicated that miR-24 high regulation is a common event in AML with t(8;21), and it might serve as a novel and selective therapeutic target for the treatment of AML with t(8;21).

Background: Human infection with avian influenza A H7N9 has emerged in China since February, 2013. The immunologic changes in pregnant women infected with H7N9 are not known. Objective: To report the clinical data and kinetic changes of immunity in a pregnant woman infected with H7N9 virus in Zhenjiang, Jiangsu, China. Methods: The clinical data were collected and immunity status was monitored in this patient. Results: H7N9 virus became undetectable in sputum from 14 days since onset of symptoms after effective antiviral therapy with oseltamivir and symptomatic/supporting treatments. The symptoms and signs in this patient gradually improved from 15 days since onset of symptoms. Peripheral lymphocytes initially decreased and gradually increased. The percentage of CD4+ T cells increased since 16 days after onset of symptoms. The kinetic changes of cytokines including IFN-γ, IFN-α, TNF-α, IL-10 and TGF-β1 matched the development and recovery of illness. Her family members, including her parents exposed to H7N9 positive materials in poultry market, were H7N9 negative. Conclusions: Our results indicate that pregnant women are susceptible to H7N9 virus and H7N9 infection in pregnant women is curable without significant impact on fetus. Kinetic changes of pro-inflammatory and anti-inflammatory cytokines play a role in the pathogenesis and clinical outcome in the pregnant patient with H7N9 infection.

The miR-98 is thought to be associated with various cancers. This study was to evaluate the potential predictive value of miR-98 expression in formalin-fixed paraffin-embedded tissue of breast cancer patients. The expression levels of miR-98 were examined in 98 breast cancer patients and 40 cancer-free controls using real-time quantitative PCR. The comparison of miR-98 expression levels between patient and control was performed using the Mann-Whitney test. The miR-98 showed higher expression levels in breast cancer patients compared with cancer free controls (p