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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
Sat Mar 02 2019
Journal Name
Biochem. Cell.arch.
EVALUATION OF PRIMARY IMPLANTS STABILITY IN IMMEDIATE AND DELAYED TREATMENT PROTOCOLS ACCORDING TO BONE DENSITY, JAWS, GENDER AND AGE UTILIZING PERIOTEST M DEVICE
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Publication Date
Fri Jun 15 2018
Journal Name
Преподаватель Xxi век
COMPARATIVE ANALYSIS OF TYPES OF METAPHORS OF RUSSIAN AND ARABIC LANGUAGES
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Metaphor is one of the most important linguistic phenomena of the artistic text, as it is the expression of the author’s emotions and evaluations, the result of a deep inner transformation of the semantic words and visual means of reflecting the national culture of each people. This paper examines the concept of linguistic metaphors and analyzes its types in the Russian and Arabic linguistics, provides a comparative analysis of metaphors in Russian and Arabic — all this allows to conclude that metaphorization is characteris- tic of different parts of speech. In the Russian language stylistic differentiation of the metaphors expressed more than in Arabic, so translation of many “sty- listic” metaphors from Russian into Arabic due to

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Publication Date
Sat Sep 30 2023
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Analysis of the tax pilot phase strategy and its impact on the tax price in Iraq
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The research aims to identify the tax policy strategy adopted in Iraq after the change of the tax system in 2003 and beyond, and then make a comparison of the two strategies on corporate data whether they are charged with progressive tax rates and after the change of the system as the tax rates became fixed, and then indicate the changes In the tax proceeds, and knowing the imensions of the approved tax policy, is it a tax reform strategy or a strategy to attract investments.The research started from the problem of exposure of the Iraqi tax system to several changes, as this led to a reflection on the technical organization of taxes, in terms of the tax rate.The descriptive analytical approach was chosen to study the actual reality of th

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Publication Date
Fri Sep 27 2019
Journal Name
Journal Of Baghdad College Of Dentistry
Clinical Assessment and Cytomorphometric Analysis of Buccal Mucosal Cells in Behçet’s Disease Patients
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Background: Behçet’s disease (BD) is a disorder of systemic inflammatory condition. Its important features are represented by recurrent oral, genital ulcerations and eye lesions. Aims. The purpose of the current study was to evaluate and compare cytological changes using morphometric analysis of the exfoliated buccal mucosal cells in Behçet’s disease patients and healthy controls, and to evaluate the clinical characteristics of Behçet’s disease. Methods. Twenty five Behçet’s disease patients have been compared to 25 healthy volunteers as a control group. Papanicolaou stain was used for staining the smears taken from buccal epithelial cells to be analyzed cytomorphometrically. The image analysis sof

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Publication Date
Mon Mar 15 2021
Journal Name
Al-adab Journal
A Socio-Pragmatic Analysis of Responses to Impoliteness in some Selected English and Arabic Literary Texts
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Publication Date
Wed Jan 11 2023
Journal Name
Modeling Earth Systems And Environment
Microfacies analysis and stratigraphic framework of the Albian succession in the low folded zone, Northern Iraq
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Publication Date
Sun Feb 28 2021
Journal Name
Iraqi Geological Journal
Facies Analysis and Depositional Stages of The Albian-Aptian Succession in Balad Oil Field, Central Iraq
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Carbonate-clastic succession which includes the Shu'aiba, Nahr Umr and Mauddud formations are representing a part of the Barremian-Aptian Sequence (Wasi'a Group). The present study includes three boreholes (Ba-1, 4 and 8) within the Balad Oil Field. The study area is located in central Iraq. This field represents a subsurface anticline with a northwest to southeast direction axis within the Mesopotamian Zone. Eight types of microfacies were recognized in the succession of the Mauddud and Shu’aiba formations. These microfacies represent shallow open marine, restricted and semi-restricted, reef - back reef, deep open marine and basinal depositional environments. While Nahr Umr Formation includes two successions, the first is the upp

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Publication Date
Fri Sep 30 2011
Journal Name
Al-khwarizmi Engineering Journal
Analysis of Temperature and Residual Stress Distribution in CO2 Laser Welded Aluminum 6061 Plates Using FEM
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This paper develops a nonlinear transient three-dimensional heat transfer finite element model and a rate independent three-dimensional deformation model, developed for the CO2 laser welding simulations in Al-6061-T6 alloy. Simulations are performed using an indirect coupled thermal-structural method for the process of welding. Temperature-dependent thermal properties of Al-6061-T6, effect of latent heat of fusion, and the convective and radiative boundary conditions are included in the model. The heat input to the model is assumed to be a Gaussian heat source. The finite element code ANSYS12, along with a few FORTRAN subroutines, are employed to obtain the numerical results. The benefit of the proposed methodology is that it

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Publication Date
Fri May 01 2015
Journal Name
2015 International Symposium On Mathematical Sciences And Computing Research (ismsc)
Analysis of significant dimensions of e-service quality in Malaysian universities
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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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