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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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Abstract<sec> <title>Background

Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.

Methods

Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro.

Results

We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.

Conclusion

Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.

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Publication Date
Wed Jun 30 2004
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Theoretical Analysis of Concentric Flow of Spherical Capsule in Laminar Flow
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Publication Date
Sun May 10 2020
Journal Name
Baghdad Science Journal
In Silico Analysis of Regulatory Elements of the Vitamin D Receptor
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Vitamin D receptor (VDR) is a nuclear transcription factor that controls gene expression. Its impaired expression was found to be related to different diseases. VDR also acts as a regulator of different pathways including differentiation, inflammation, calcium and phosphate absorption, etc. but there is no sufficient knowledge about the regulation of the gene itself. Therefore, a better understanding of the genetic and epigenetic factors regulating the VDR may facilitate the improvement of strategies for the prevention and treatment of diseases associated with dysregulation of VDR. In the present investigation, a set of databases and methods were used to identify putative functional elements in the VDR locus. Histone modifications, CpG I

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Publication Date
Wed Mar 29 2023
Journal Name
Journal Of The College Of Education For Women
Geographical Analysis of Sanitation Workers in the Urban District of Kut
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Cleaning is one of the services provided by the state and its ad hoc institutions. Every developed country is clean due to the good planning and attention given to the staff of all municipalities and service institutions. Beside, the attention paid to this sector is considered one of the windows to maintain the states’ aesthetics. If janirtos stop disposing of all the discarded wastes, the result will be having big piles of waste, affecting accordingly the health and safety of its citizens and the aesthetics of the areas. The janitors and those responsible for them are tha staff that the state must take care of because of their importance to the state in general and to the province in particular. The importance of the research

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Publication Date
Sat Dec 14 2019
Journal Name
Journal Of The College Of Education For Women
Analysis of the Structure of Scientific News Headlines in Online Newspapers
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Newspaper headlines are described as compressed and ambiguous pieces of discourse that represent the bodies of the articles. Their main function is to provide the readers with an informative message they would have no prior idea about. Ifantidou (2009) claims that the function of a headline is to get the readers’ attention rather than providing information because it does not have to represent the whole of the article it refers to. This paper aims at examining this hypothesis in relation to scientific news headlines reported by a number of news agencies. The paper follows Halliday (1967) information structure theory by applying it on ten selected headlines; each two headlines represent one scientific discovery reported by different new

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Publication Date
Mon May 01 2017
Journal Name
2017 5th International Conference On Information And Communication Technology (icoic7)
Analysis of the number of ants in ant colony system algorithm
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Publication Date
Wed Feb 11 2015
Journal Name
Journal Of Kerbala University
Histological study for effct of Carbamazepine drug on the developing brain at day 13 of pregnancy of Mus musclus
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Epilepsy is considered as one of the common neurological disorders.About 50 million persons have affected by epilepsy .Carbamazepine is one of the common drugs used by pregnant women with epilepsy. The aim of the present study is to investigate the effect of carbamazepine on the process of brain development during day 13 of pregnancy.Fifty pregnant albino mice have been used. They were divided into two groups. The control group that had been orally drenched with normal saline. The other group was treated group that had been given 15 mgKg of Carbamazepine orally. The fetuses have been collected after killing of the mice. Boun’s solution was selected as fixative. 5-8 µm thick sections from the fetuses were cut to be stained with hematoxyli

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Publication Date
Sun Jun 01 2025
Journal Name
Journal Of University Of Anbar For Pure Science
SARS-CoV-2 history, diagnosis, genetic diversity and treatment: a comprehensive review
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This article comprehensively examines the history, diagnosis, genetics, diversity, and treatment of SARS-CoV-2. It details the emergence of coronaviruses over the past 50 years, including the coronavirus from 2019 and its subsequent mutations, along with updated information about this virus. This review explains the development and nomenclature of coronaviruses, their cellular invasion through glycoprotein spikes binding to ACE-2 receptors, and the mechanism of cell entry via endocytosis. Diagnosis methods for COVID-19, including nucleic acid amplification, serology, and imaging techniques like chest X-ray and CT scan tests, are discussed. Treatment approaches for COVID-19 are outlined, emphasizing healthcare, antiviral medications like Rem

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Publication Date
Thu Jun 30 2016
Journal Name
Al-kindy College Medical Journal
Secondary skull tumors: Prevalence, MRI findings as a diagnostic tool, and treatment
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Background: Skull secondary tumors are malignant bone tumors which are increasing in incidence.Objective: The objectives of this study were to present clinical features , asses the outcome of patients with secondary skull tumors ,characterize the MRI features, locations, and extent of secondary skull tumors to determine the frequency of the symptomatic disease.Type of the study: This is a prospective study.Methods: This is a prospective study from February 2000 to February 2008. The patients were selected from five neurosurgical centers and one oncology hospital in Baghdad/Iraq. The inclusion criteria were MRI study of the head(either as an initial radiological study or following head CT scan when secondary brain tumor is suspected , vis

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Publication Date
Sun Jun 01 2025
Journal Name
Journal Of University Of Anbar For Pure Science
SARS-CoV-2 history, diagnosis, genetic diversity and treatment: a comprehensive review
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Publication Date
Sat Dec 04 2021
Journal Name
Ournal Of Global Trends In Pharmaceutical Sciences
REVIEW ARTICLE: COVID – 19: INFECTION, ORIGIN, TRANSMISSION, DIAGNOSIS, TESTS AND TREATMENT OPTIONS
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