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Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non-amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate-limiting step for amyloid-ß production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1-mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.

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Acute myeloid leukemia (AML) shows multiple chromosomal translocations & point mutations which can be used to refine risk-adapted therapy in AML patients. Ecotropic viral integration site-1 (EVI-1) & myocyte enhancer factor 2 C gene (MEF2C) are key regulatory transcription factors in hematopoiesis and leukemogenesis & both drive immune escape. This prospective study involved 80 adult de novo AML patients recruited from Oncology Center, Mansoura University, between March 2019 and July 2021. The MEF2C and EVI1 expression were measured using a Taqman probe-based qPCR assay. The results revealed that EVI1 and MEF2C expression were significantly elevated in AML patients as compared to control subjects (p = 0.001. 0.007 respectively). Aberrant expressions of EVI1 and MEF2C showed a significant negative correlation with hemoglobin levels (p = 0.034, 0.025 respectively), & bone marrow blasts (p = 0.007, 0.002 respectively). 11q23 translocation was significantly associated with EVI1 and MEF2C (p = 0.004 and 0.02 respectively). Also, t (9;22) was significantly associated with EVI1 and MEF2C (p = 0.01 and 0.03 respectively), higher expression of EVI1 and MEF2C were significantly associated with inferior outcome after induction therapy (p = 0.001 and 0.018 respectively) and shorter overall survival (p = 0.001, 0.014 respectively). In conclusion, EVI1 & MEF2C were significantly expressed in AML cases. EVI1 & MEF2C overexpression were significantly associated with 11q23 rearrangements and t (9;22) and were indicators for poor outcome in adult AML patients; These results could be a step towards personalized therapy in those patients.

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Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, for the Transwell cell migration and invasion assay experiments shown in Fig. 3 on p. 1650, there were several panels showing overlapping sections of data; moreover, certain of the data shown in this Figure were also strikingly similar to data appearing in different form in Fig. 4 in another article written by different authors at a different research institute [Liu J and Duan X: PA­MSHA induces apoptosis and suppresses metastasis by tumor associated macrophages in bladder cancer cells. Cancer Cell Int 17: 76, 2017].  Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 1645­1653, 2019; DOI: 10.3892/mmr.2018.9796].

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INTRODUCTION: AML patients with KMT2A-MLLT3 and other 11q23 abnormalities belong to the intermediate and high-risk level groups, respectively. Whether the poor prognostic value of Ecotropic Viral Integration site-1 (EVI1) overexpression suits either the subtypes of KMT2A-MLLT3 or Non-KMT2A-MLLT3 AML patients (intermediate and high risk group) needs to be further investigated. METHODS: We retrospectively analyzed the clinical characteristics of 166 KMT2A-r and KMT2A-PTD AML patients. RESULTS: For the Non-KMT2A-MLLT3 group, patients in the EVI1-high subgroup had shorter OS and DFS and higher CIR than those in the EVI1-low subgroup (p = .027, p = .018, and p = .020, respectively). Additionally, both KMT2A-MLLT3 and Non-KMT2A-MLLT3 patients who received chemotherapy alone had poorer prognosis than patients who also received allogeneic hematopoietic stem cell transplant (allo-HSCT) regardless of their EVI1 expression level (all p < .001). For transplanted patients with KMT2A-MLLT3 or Non-KMT2A-MLLT3 rearrangement, the EVI1-high subgroup had worse prognosis than the EVI1-low subgroup (all p < .05). The 2-year CIR of the KMT2A-MLLT3 and Non-KMT2A-MLLT3 groups with high EVI1 expression was high (52% and 49.6%, respectively). However, for patients with low EVI1 expression, the 2-year CIR of transplanted patients with KMT2A-MLLT3 and Non-KMT2A-MLLT3 was relatively low. CONCLUSIONS: Our study showed that for the Non-KMT2A-MLLT3 group, the EVI1-high group had shorter OS and DFS than the EVI1-low group. High EVI1 expression showed an adverse effect in AML with KMT2A rearrangement in different risk stratification subtypes. For the EVI1-high patients with non-KMT2A-MLLT3 rearrangement, other novel regimens towards relapse should be taken into consideration.

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Nasopharyngeal carcinoma (NC) arises from the nasopharynx epithelium and the majority of NC cases globally are within China and Southeast Asia. Both short palate lung and nasal epithelium clone 1 (SPLUNC1) and myelodysplasia syndrome 1-ectopic viral integration site 1 (MDS1-EVI1) play an important role in carcinogenesis and have been found to be associated with nasopharyngeal carcinoma. In spite of their role in NC, the association between these genes and their polymorphisms in the development of NC has thus far not been studied. In the present study, the relationship between SPLUNC1 (rs2752903, T>C) and MDS1-EVI1 (rs6774494, G>A) polymorphisms and their role in the development of NC among the Chinese population were investigated. From a Chinese population of 1,059 patients with NC and 891 controls, genotype frequencies and the distribution of SPLUNC1 and MDS1-EVI1 polymorphisms were analyzed for possible susceptibility to NC. It was observed that those with MDS1-EVI1 CC (OR, 2.76; 95% CI, 1.96-3.81) and MDS1-EVI1 CT (OR, 1.51; 95% CI, 1.22-2.14) polymorphisms had an increased risk of developing NC. Those with SPLUNC1 AA genotypes also observed a higher risk for NC compared with SPLUNC1 GG genotypes (OR, 2.15; 95% CI, 1.62-3.15). When observing the gene-gene interaction between SPLUNC1 and MDS1-EVI1 polymorphisms, it was found that the presence of both SPLUNC1 CC and MDS1-EVI1 AA alleles was associated with a higher risk for NC compared with those who did not carry both alleles (OR, 6.75; 95% CI, 3.41-12.11). The present study suggested that the association between SPLUNC1 (rs2752903, T>C) and MDS1-EVI1 (rs6774494, G>A) polymorphisms may be a potent risk factor in the occurrence of NC.

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BACKGROUND: The myeloid ecotropic viral integration site (MEIS) family of genes is related to the occurrence, development, and outcome of many cancers. However, its role in the immune and tumor microenvironment (TME) is unclear. This study explored the relationship between the expression of MEIS genes and patient survival, immune subtypes, TME, tumor stem cell correlation, and drug sensitivity in cancer. METHODS: We used The Cancer Genome Atlas pan-cancer data to analyze the expression of the MEIS family genes. Kaplan-Meier analysis and univariate Cox proportional hazard regression model were used to detect the relationship between gene expression and overall survival. Analysis of variance was used to explore the relationship between the MEIS family and the immune components in the tumor, and the ESTIMATE algorithm was used to calculate the proportion and level of tumor-infiltrating immune cells. Spearman and Pearson's correlation tests were carried out to detect the relationship between MEIS and the characteristics of tumor stem cells and drug sensitivity. RESULTS: The MEIS family of genes shows different expression profiles in different cancers, with substantial inter- and intra-cancer heterogeneity. Among them, MEIS3 was upregulated in most cancers, whereas MEIS2 was downregulated. The change in MEIS gene expression was usually related to overall survival, but whether a member of the MEIS family was a risk factor or a protective factor was cancer-dependent. Immune component analysis suggested that the role of MEIS genes in promoting or inhibiting cancer may be related to different degrees of immune silencing. Further, there were varying degrees of correlation between MEIS gene expression and cancer cell stemness characteristics. It was also found that MEIS genes, especially MEIS1 and MEIS2, may be related to chemotherapy resistance. CONCLUSIONS: We explored the expression, prognostic relationship, molecular characteristics, and effects on immunity and TME of the MEIS gene family in cancer. Our results suggest that MEIS members should be studied as independent entities in different types of cancer. The MEIS gene family may be a potential target for cancer therapy, but further experiments are needed to confirm this.

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OBJECTIVES: To evaluate the expression of myeloid ecotropic viral integration site 1 (Meis1) and vascular endothelial growth factor receptor 2 (VEGFR-2) in early-stage kidney cancers and the clinical significance. METHODS: The cancer tissues and the matched adjacent normal tissues in patients with kidney cancer, who received surgical treatment from April 2005 to September 2018 in the Haikou Hospital Affiliated to Xiangya School of Medicine, Central South University, were collected. The samples included 80 pairs of paraffin specimen, 15 pairs of fresh cancer and the matched adjacent normal tissues from these patients. Real-time PCR and immunohistochemical method were used to detect the expression levels of Meis1 and VEGFR-2 mRNA and protein in kidney tissues and adjacent normal tissues, and the correlation of clinical pathology parameters and the prognosis were analyzed in the patients. RESULTS: The expression levels of Meis1 and VEGFR-2 mRNA and protein in the renal carcinoma tissues were lower than those in the matched adjacent normal tissues (both P<0.01), and the expression levels of Meis1 were positively correlated with that of VEGFR-2 (r=0.681, P<0.01). The analysis of relevant clinical-pathological parameters in the patients showed that: the expression positive rate of Meis1 was significantly related with the pathological type of renal cancer (P<0.01), while the positive rate of Meis1 and VEGFR-2 expression was not related with the gender, age, T stage of patients (all P>0.05), but it was significantly related with the prognosis in the patients (P<0.05). Cox regression analysis showed that: Meis1 was an independent factor for the prognosis of patients (P<0.05). CONCLUSIONS: The mRNA and protein expression levels of Meis1 and VEGFR-2 in the early-stage kidney cancer tissues are significantly decreased compared with those in the adjacent normal tissues. Meis1 may be served as a tumor suppressor to affect the occurrence and development of kidney cancer. Therefore, Meis1 may be used as a biomarker to predict the prognosis of patients with kidney cancer.

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AIM: Proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are regarded as the primary factors resulting in pulmonary arterial remodeling in pulmonary hypertension (PH). Myeloid ecotropic viral integration site 1 (MEIS1) has been positioned as a negative cardiomyocyte cell cycle regulator and regulates proliferation of multiple kinds of cancer cells. Whether MESI1 is involved in the proliferation and migration of PASMCs deserves to be identified. MAIN METHODS: Sprague Dawley rats were exposed to hypoxia condition (10% O2) for 4 weeks to induce PH and primary rat PASMCs were cultured in hypoxia condition (3% O2) for 48 h to induce proliferation and migration. Immunohistochemistry, immunofluorescence, reverse transcription PCR and Western blot analysis were performed to detect the expressions of target mRNAs and proteins. EDU, CCK8 and wound healing assays were conducted to measure the proliferation and migration of PASMCs. KEY FINDINGS: Hypoxia down-regulated the expression of MEIS1 (both mRNA and protein) in pulmonary arteries and PASMCs. Over-expression of MEIS1 inhibited the proliferation and migration of PASMCs afforded by hypoxia. In contrast, knockdown of MEIS1 under normoxia condition like hypoxia induced the proliferation and migration of PASMCs. MEIS1 mediated hypoxia-induced the proliferation and migration of PASMCs via METTL14/MEIS1/p21 signaling. SIGNIFICANCE: The present study revealed that MEIS1 regulated the proliferation and migration of PASMCs during hypoxia-induced PH. Thus, MEIS1 may be a potential target for PH therapy.

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Although ecotropic viral integration site 2 A (EVI2A) plays key roles in several cancers, the expression and function of EVI2A in osteosarcoma (OS) have not been investigated. Hence, we explored the expression of EVI2A and its clinical significance of EVI2A of OS. Firstly, we investigated the expression of EVI2A in OS tissues. The relationship of EVI2A expression and survival time was analyzed using Kaplan-Meier plotter. Then, we used quantitative reverse transcription PCR (qRT-PCR) to confirm the expression level of EVI2A in OS cell lines. Cell proliferation, and wound-healing experiments were used to identify the biological function of EVI2A. Moreover, EVI2A-mediated MEK/ERK signaling pathway was evaluated using western blotting. Data suggested that EVI2A was highly expressed in OS tissues, and high-expression of EVI2A was associated with worse overall survival in OS patients. Moreover, the up-regulation of it was observed in OS cell lines (Saos2, and MG63). Knockdown of EVI2A suppressed cell proliferation and migration of OS. Western blotting revealed that the inactivation of MEK/ERK pathway was found in OS cells after EVI2A knockdown. Our data implicated the crucial role of EVI2A in the progression of OS, demonstrating that expression of EVI2A may offer an attractive novel prognostic signature for OS.

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PURPOSE: Ecotropic viral integration site-1 (EVI1) is a transcription factor that contributes to the unfavorable prognosis of leukemia, some epithelial cancers, and glial tumors. However, the biological function of EVI1 in glioblastoma multiforme (GBM) remains unclear. Based on microarray experiments, EVI1 has been reported to regulate epidermal growth factor receptor (EGFR) transcription. Signal transduction via EGFR plays an essential role in glioblastoma. Therefore, we performed this study to clarify the importance of EVI1 in GBM by focusing on the regulatory mechanism between EVI1 and EGFR transcription. METHODS: We performed immunohistochemical staining and analyzed the EVI1-expression in glioma tissue. To determine the relationship between EVI1 and EGFR, we induced siRNA-mediated knockdown of EVI1 in GBM cell lines. To investigate the region that was essential for the EVI1 regulation of EGFR expression, we conducted promoter reporter assays. We performed WST-8 assay to investigate whether EVI1 affected on the proliferation of GBM cells or not. RESULTS: It was observed that 22% of GBM tissues had over 33% of tumor cells expressing EVI1, whereas no lower-grade glioma tissue had over 33% by immunohistochemistry. In A172 and YKG1 cells, the expression levels of EGFR and EVI1 correlated. Analysis of the EGFR promoter region revealed that the EGFR promoter (from - 377 to - 266 bp) was essential for the EVI regulation of EGFR expression. We showed that EVI1 influenced the proliferation of A172 and YKG1 cells. CONCLUSION: This is the first study reporting the regulation of EGFR transcription by EVI1 in GBM cells.

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The retrovirus human T-cell leukemia virus type 1 (HTLV-1) integrates into the host DNA, achieves persistent infection, and induces human diseases. Here, we demonstrate that viral DNA-capture sequencing (DNA-capture-seq) is useful to characterize HTLV-1 proviruses in naturally virus-infected individuals, providing comprehensive information about the proviral structure and the viral integration site. We analyzed peripheral blood from 98 naturally HTLV-1-infected individuals and found that defective proviruses were present not only in patients with leukemia, but also in those with other clinical entities. We further demonstrated that clones with defective-type proviruses exhibited a higher degree of clonal abundance than those with full-length proviruses. The frequency of defective-type proviruses in HTLV-1-infected humanized mice was lower than that in infected individuals, indicating that defective proviruses were rare at the initial phase of infection but preferentially selected during persistent infection. These results demonstrate the robustness of viral DNA-capture-seq for HTLV-1 infection and suggest potential applications for other virus-associated cancers in humans.

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Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic progenitor cells and the most common malignant myeloid disorder in adults. Several gene mutations such as in NPM1 (nucleophosmin 1) are involved in the pathogenesis and progression of AML. The aim of this study was to identify genes whose expression is associated with driver mutations and survival outcome. Genotype data (somatic mutations) and gene expression data including RNA-seq, microarray, and qPCR data were used for the analysis. Multiple datasets were utilized as training sets (GSE6891, TCGA, and GSE1159). A new clinical sample cohort (Semmelweis set) was established for in vitro validation. Wilcoxon analysis was used to identify genes with expression alterations between the mutant and wild type samples. Cox regression analysis was performed to examine the association between gene expression and survival outcome. Data analysis was performed in the R statistical environment. Eighty-five genes were identified with significantly altered expression when comparing NPM1 mutant and wild type patient groups in the GSE6891 set. Additional training sets were used as a filter to condense the six most significant genes associated with NPM1 mutations. Then, the expression changes of these six genes were confirmed in the Semmelweis set: HOXA5 (P = 3.06E-12, FC = 8.3), HOXA10 (P = 2.44E-09, FC = 3.3), HOXB5 (P = 1.86E-13, FC = 37), MEIS1 (P = 9.82E-10, FC = 4.4), PBX3 (P = 1.03E-13, FC = 5.4) and ITM2A (P = 0.004, FC = 0.4). Cox regression analysis showed that higher expression of these genes - with the exception of ITM2A - was associated with worse overall survival. Higher expression of the HOX genes was identified in tumors harboring NPM1 gene mutations by computationally linking genotype and gene expression. In vitro validation of these genes supports their potential therapeutic application in AML.

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Acute myeloid leukemia (AML) is a type of malignant tumor that is caused by malignant clone hematopoietic stem cells. The ecotropic viral integration site 1 (Evi1) is a zinc finger transcription factor, which is highly expressed in AML, and its expression level has been associated with poor prognosis of AML. Previous studies have indicated that Evi1 may regulate cell proliferation, differentiation and apoptosis by inhibiting the membrane-spanning-4-domains subfamily-A member-3 (MS4A3) gene in AML. The aim of the present study was to investigate the role of Evi1 in the progression of AML. The results revealed that Evi1 was overexpressed in leukemia cells compared with normal T lymphocytes. MicroRNAs (miR)-133 and -431 that target Evi1 were investigated, and it was observed that there was a low expression of miR-431 in AML. The transfection of miR-431 was able to decrease the promoter methylation levels of the Evi1 gene in AML cells. The transfection of miR-431 also suppressed the migration and invasion of AML cells. The present study revealed that the transfection of miR-431 mimic was able to downregulate MS4A3 expression in AML cells. Furthermore, the expression levels of transforming growth factor ß (TGFß) and epithelial-to-mesenchymal transition (EMT) markers fibronectin, α-smooth muscle actin, and vimentin were downregulated following the transfection of miR-431 in AML cells. The overexpression of MS4A3 was also able to suppress miR-431-mediated inhibition of the expression of TGFß and EMT markers in AML cells. The addition of TGFß inhibited the downregulation of EMT markers by transfection of miR-431 in AML cells. The transfection of miR-431 suppressed the migration and invasion of AML cells, which was also abolished by the addition of TGFß. In conclusion, the results of the present study indicated that Evi1 may be a potential molecular target of leukemia therapy via MS4A3-mediated TGFß/EMT signaling pathway.

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Objective To investigate the regulation mechanism of microRNA - 9(miR - 9)by ecotropic viral integration site1(EVI1)its impact on proliferation of AML cells and its role in the pathogenesis of myelogenous leuke-mia. Methods EVI1 was forced to express in Uocm1 cell lines by murine stem cell virus - EVI1(MSCV - EVI1) plasmid infection. EVI1 overexpressed Uocm1 cells were then treated with 0. 1 μmol/ L 5 - aza - 2′ - deoxycytidine (5 - AZA)dissolved in dimethyl sulfoxide (DMSO). The methylation level of miR - 9 promoter was tested by DNA bi-sulfite sequencing technology. The cell cycle was observed by flow cytometry (FCM). The proliferation ability of the cells was detected by the colony forming assay in semi - solid Methylcellulose medium culture. Results EVI1 level was dramatically increased after being infected by MSCV - EVI1 plasmid. Forced expression of EVI1 in Uocm1 signifi-cantly downregulated miR - 9 by inducing hypermethylation of miR - 9 promoter. Relative expression level of miR - 9 was lower in EVI1 overexpressed group(0. 004 ± 0. 000)than that of the control group(0. 006 ± 0. 001)(t = 4. 09,P <0. 05). When EVI1 was overexpressed in Uocm1,the rate of G0 / G1 cells decreased markedly(P < 0. 05),while rates of S phage and G2 phage increased significantly(all P < 0. 05). Seven days after 500 cells plated in semi - solid medium, EVI1 overexpressed Uocm1 cells gave rise to more colony (122. 3 ± 7. 8)than Uocm1 cells infected with vector (45. 7 ± 6. 1)(t = - 13. 44,P < 0. 01). 0. 1 μmol/ L 5 - AZA recovered miR - 9 expression(P < 0. 01)by decreasing EVI1 induced hypermethylation of miR - 9 promoter. G0 / G1 phase cell proportion was(48. 25 ± 2. 19)％ in control group,while (65. 90 ± 2. 90)％ in 5 - AZA group (t = - 6. 85,P < 0. 05). 5 - AZA group formed less colony (51. 00 ± 10. 01)than the control group (123. 40 ± 8. 12)(t = 9. 59,P < 0. 01),which indicated that 5 - AZA inhibi-ted cell proliferation by G0 / G1 cell cycle retardation in EVI1 overexpressed uocm1 cells. Conclusions EVI1 may en-hance proliferation ability of myeloid leukemia cells by downregulating miR - 9 through inducing hypermethylation of miR - 9 promotor,which plays a crucial role in the pathogenesis of AML. 5 - AZA may be an effective hypomethylating agent in the therapy of EVI1 high acute myeloid leukemia.

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AIM: To explore the expression and clinical significance of ecotropic viral integration site-1 (EVI1) of lung squamous cell cancer (SCC). METHODS: The expression of EVI1 in SCC was detected by immunohistochemistry and the validation cohort was divided into EVI1 high-expression group and low-expression group according to the cutoff of immunohistochemical score. The correlations between EVI1 expression and the clinicopathological factors were analyzed by χ2 test. The relation between EVI1 expression and overall survival rate was evaluated by univariate analysis with Kaplan-Meier method. The independent prognostic factor was identified by multivariate analysis with Cox regression model. RESULTS: In this study, the EVI1 high-expression percentage was 32.32% (53/164). EVI1 high expression was significantly associated with a poorer overall 5-year survival rate of SCC (P=0.021). Moreover, EVI1 high expression was identified as an independent prognostic factor of SCC, predicting the unfavorable prognosis (P=0.013). CONCLUSION: High expression of EVI1 was significantly associated with a poorer prognosis and it was identified as an independent prognostic factor of SCC.

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As an proto-oncogene,ecotropic viral integration site 1 (EVI1) gene is over-expressed in acute myeloid leukemia (AML) because of chromosomal translocation or other genetic abnormalities,finally cause poor prognosis.In recent years,an increasing research of the expression of EVI1 in acute lymphoblastic leukemia (ALL),especially in pediatric ALL.The overexpression of EVI1 gene also suggest a poor prognosis,which is closely relate to the age.But the relationship between the expression of EVI1 gene and mixed lineage leukemia (MLL) and BCR-ABL gene rearrangement needs to be further studied.Researching the expression of EVI1 gene in ALL and exploring targeted therapeutic agents are important research directions in the future.

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As an proto-oncogene,ecotropic viral integration site 1 (EVI1) gene is over-expressed in acute myeloid leukemia (AML) because of chromosomal translocation or other genetic abnormalities,finally cause poor prognosis.In recent years,an increasing research of the expression of EVI1 in acute lymphoblastic leukemia (ALL),especially in pediatric ALL.The overexpression of EVI1 gene also suggest a poor prognosis,which is closely relate to the age.But the relationship between the expression of EVI1 gene and mixed lineage leukemia (MLL) and BCR-ABL gene rearrangement needs to be further studied.Researching the expression of EVI1 gene in ALL and exploring targeted therapeutic agents are important research directions in the future.

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UNLABELLED: The involvement of the hepatitis B virus X (HBx) protein in epigenetic modifications during hepatocarcinogenesis has been previously characterized. Long noncoding RNAs (lncRNAs), a kind of epigenetic regulator molecules, have also been shown to play crucial roles in HBx-related hepatocellular carcinoma (HCC). In this study, we analyzed the key transcription factors of aberrantly expressed lncRNAs in the livers of HBx transgenic mice by bioinformatics prediction, and found that ecotropic viral integration site 1 (Evi1) was a potential main transcription regulator. Further investigation showed that EVI1 was positively correlated to HBx expression and was frequently up-regulated in HBV-related HCC tissues. The forced expression of HBx in liver cell lines resulted in a significant increase of the expression of EVI1. Furthermore, suppression of EVI1 expression decreased the proliferation of HCC cells overexpressing HBx in vitro and in vivo. CONCLUSION: Our findings suggest that EVI1 is frequently up-regulated and regulates a cluster of lncRNAs in HBV-related hepatocellular carcinoma (HCC). These findings highlight a novel mechanism for HBx-induced hepatocarcinogenesis through transcription factor EVI1 and its target lncRNAs, and provide a potential new approach to predict the functions of lncRNAs.

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Chronic neutrophilic leukemia (CNL) is a rare type of myeloproliferative neoplasm, characterized by sustained neutrophilia, splenomegaly, bone marrow granulocytic hyperplasia (without evidence of dysplasia) and an absence of the Philadelphia chromosome. Thus far, ~150 cases of CNL have been described in the literature; however, none have demonstrated overexpression of the ecotropic viral integration site-1 (EVI-1, also known as MECOM) gene. The present study describes a case that fulfilled the World Health Organization diagnostic criteria for CNL, and was associated with overexpression of EVI-1, as well as novel concurrent mutations of colony stimulating factor 3 receptor (CSF3R) and SET binding protein-1 (SETBP1). In addition, the current study briefly reviewed the relevant literature regarding novel genetic findings associated with the diagnosis and treatment of CNL. To the best of our knowledge, this is the first case report of CNL with associated EVI-1 overexpression, and concurrent CSF3R and SETBP1 mutations.

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Viral integration into the human genome upon infection is an important risk factor for various human malignancies. We developed viral integration site detection tool called Virus-Clip, which makes use of information extracted from soft-clipped sequencing reads to identify exact positions of human and virus breakpoints of integration events. With initial read alignment to virus reference genome and streamlined procedures, Virus-Clip delivers a simple, fast and memory-efficient solution to viral integration site detection. Moreover, it can also automatically annotate the integration events with the corresponding affected human genes. Virus-Clip has been verified using whole-transcriptome sequencing data and its detection was validated to have satisfactory sensitivity and specificity. Marked advancement in performance was detected, compared to existing tools. It is applicable to versatile types of data including whole-genome sequencing, whole-transcriptome sequencing, and targeted sequencing. Virus-Clip is available at http://web.hku.hk/~dwhho/Virus-Clip.zip.

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