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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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 30 2002
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
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Publication Date
Sun Mar 06 2016
Journal Name
Baghdad Science Journal
Synthesis and Characterization of 3 - Substituted Coumarin

The reaction of(2-oxo-2H-chromen-3-Carbonyl chloride)(k1) with hydrazine in boiling ethanol gives the hydrazide(K2).When compound (k2) reacts with various aromatic aldehydes ,the corres ponding Schiff bases(k3–k4) achieve new series of thiazotidines (k5–k6) and azetidinones (k7–k8) obtained from the reactions of appropriate Schiff bases with mercapto acetic acid and chloro acetyl chloride respectively. All the compounds are characterized by FT-IR,1H-NMR and GC-Ms.

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Publication Date
Wed Dec 13 2017
Journal Name
Al-khwarizmi Engineering Journal
Synthesis and Characterization of Nanocrystalline Zeolite Y

Worldwide attention is being focused on  nanocrystalline  zeolites  and they are replacing conventional ones due to their pronounced potential in many fields. In this study, NaY zeolite has been prepared hydrothermally using sol –gel method and modified to the proton type by ion –exchange process. Characterization is made using X-ray diffraction (XRD), thermogravimetric analysis (TGA),  Fourier transform infrared spectroscopy (FTIR),  Atomic force microscopy (AFM), Brunauer –Emmet- Teller (BET) nitrogen adsorption method, Ammonia Temperature programmed desorption (NH3-TPD) and Scanning electron microscopy( SEM).  The effect of aging time, silica to alumina ratio is studied and the results sh

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Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Synthesis and Characterization of New Thioxanthone Derivatives

This work comprises the synthesis of new thioxanthone derivatives containing C-substituted thioxanthone. To obtain these derivatives, the o-mercapto benzoic acid was chosen as the starting material, which was reacted with dry benzene in sulfuric acid (98 %) to produce the thioxanthone (1). The 2,7-(disulfonyl phosphine imine) thioxanthone (4-8) were prepared from reaction of compound (1) with chlorosulfonic acid gave 2,7-(disulfonyl chloride) thioxanthone (2). Treatment of (2) with sodium azide to produce 2,7-(disulfonyl azide) thioxanthone (3). Condensation of (3) with phosphorus compounds afforded compounds (4-8). The 2,7-(disulfonamide) thioxanthone (9-21) was obtained when co

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Publication Date
Fri Jan 26 2024
Journal Name
Iraqi Journal Of Science
Seismicity Evaluation of Central and Southern Iraq

This study covers the area bounded by latitudes 29° to 34° N and longitudes 39° to 48°E.The seismicity of area for the period 1980–2011 is evaluated. In this study the geological and topography were performed, regarding the historical seismicity. More than (145) events were re-analyzed in Iraqi Seismological Network (ISN) and the recorded data was subjected to statistical analysis. This study shows high activity in the east and very low activity in the west.

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Publication Date
Tue Sep 19 2017
Journal Name
Al-academy
Pen weight and diversity of Arabic calligraphy

           This thesis study (pen weight and diversity of Arabic calligraphy), including the Arabic script went through multiple bodies, it came through the natural evolution of societies, and helped in the renovation and development of calligraphy after they gained a clear identity as a result of development that has occurred in the materials and writing instruments, especially industry pen that led to the diversity of Arabic calligraphy, and through the exploratory research and modeling study, which was obtained that the researcher could pose a problem discussed in the first chapter of his study follows by asking: is the pen is the weight of the role in the diversity of Arabic calligrap

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Publication Date
Fri Jun 24 2022
Journal Name
Iraqi Journal Of Science
Antibacterial and Antibiofilm Activity of Flaxseed Oil

The present study aimed to explore the antibacterial and antibiofilm activity of flaxseed oil on some locally isolated bacterial pathogens. No inhibitory effect was noticed against Escherichia coli or Enterococcus faecalis. However, variable effects were developed against Methicillin resistant Staphylococcus aureus (MRSA), methicillin sensitive Staphylococcus aureus (MSSA), Klebsiella pneuminae and Staphylococcus epidermidis. The flaxseed exhibited antibiofilm activity against all tested bacterial isolates (MSSA, MRSA, S. epidermidis and K. pneumoniae) and showed various degrees of inhibition against them. Experimental wounds were healed by application of flaxseed oil. In conclusion, flaxseed oil is a good alternative medication can be u

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Publication Date
Wed Apr 01 2009
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Thyroid Disorders and the Level of Malondialdehyde

Background: Free radicals have been implicated in many pathological processes, including ischemia, inflammation, and malignancy. The free radicals may affect tissues damage by lipid
peroxidation which generate malondialdehyde (MDA) as a by byproduct of the reaction. The objective of this study is to examine the dynamics of lipid peroxidation in patients with
thyroid disorders using the measurement of malondialdehyde level as a marker for the degree of thyroid disorder.
Methods: Two hundred and forty five subjects were enrolled in this study. Hundred and ninety five were patients with different thyroid disorders (88 yperthyroidism, 63 hypothyroidism and 44 thyroid carcinoma) the remaining 50 subjects were

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Publication Date
Thu Feb 01 2024
Journal Name
Baghdad Science Journal
Forgotten Index and Forgotten Coindex of Graphs

F index is a connected graph, sum of the cubes of the vertex degrees. The forgotten topological index has been designed to be employed in the examination of drug molecular structures, which is extremely useful for pharmaceutical and medical experts in understanding the biological activities. Among all the topological indices, the forgotten index is based on degree connectivity on bonds. This paper characterized the forgotten index of union of graphs, join graphs, limits on trees and its complements, and accuracy is measured. Co-index values are analyzed for the various molecular structure of chemical compounds

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Publication Date
Mon Mar 01 2010
Journal Name
Al-khwarizmi Engineering Journal
Components and Treatments of Oilfield Produced Water

In this study, a review of variety of processes that are used in the treatment produced water prior to reuse or to responsible disposal are presented with their environmental issues and economical benefits. Samples of produced water from five locations in Rumaila oilfield/in south of Iraq were taken and analyzed for their contents of brine, some heavy metals, total suspended solids and oil and grease. Moreover, two samples of water were treated using reverse osmosis technique which showed its ability to treat such contaminated water. The results showed that the environmental impact of produced water arises from its chemical composition; i.e., its salt content, its heavy metals, and hydrocarbon contents.

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