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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 Oct 12 2019
Journal Name
Journal Of The College Of Education For Women
Participatory Planning and Sustainable Development of Society

 

Community participation is one of the basic pillars of the sustainable development process. It provides opportunities for different groups of society to contribute to the management, preparation and implementation of development plans commensurate with their needs and aspirations. In this context, the study presents a study of the concept of community participation and its importance in sustainable development, In terms of its conditions, requirements and principles, as well as its image, as well as addressing the most important challenges and obstacles facing the participation of citizens in development projects. The research also provides an analysis of a number of international and Arab experiences adopted In its polici

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Publication Date
Wed Aug 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
(Energy alternatives and the possibility of substitution)

Many of the signs that the global energy system indicate the start of a period of transition from total dependence on fossil energy sources, especially oil, into a new era in which alternative energy sources play an important role in meeting the growing needs of energy demand, so sought many of the developed countries through research the studies carried out to try to bring renewable energy sources and non-renewable (shale oil, oil sands, solar energy, wind energy .... etc) replace traditional fossil energy sources (oil, gas, coal) and despite the recent availability dramatically and spread throughout the the world, but they are going to dry up in the foreseeable future. So many countries, especially the developed sought to find

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Publication Date
Sun Mar 01 2009
Journal Name
Al-khwarizmi Engineering Journal
Monitoring and Quality Control of Stud Welding

This study is conducted to carry out a straightforward way appropriate for quality monitoring and stability of arc stud welding process, followed by a number of procedures to control the quality of welded samples, namely torque destructive testing and visual inspection context.  Those procedures were being performed to support the monitoring system and verify its validity. Thus, continuous on-line monitoring guarantees earlier discovering stud welding defects and avoiding weld repeatability. On-line welding electronic monitoring system is for non destructive determining if a just completed weld is satisfactory or unsatisfactory, depending on welding current peak value detected by the system. Also, it has been observed significant ha

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Publication Date
Wed Jun 04 2008
Journal Name
Ibn Al-haitham Journal For Pure And Applied Science
Synthesis and characterization of new ligand c

In the present paper we report the synthesis of a new ligand [HL][(2-1-[(2-hydroxy-benzylidene)-hydrazono]-ethyl) benzene-1, 3, 5-triol and its complexes with (Mn", Fe", Cd", and Hg") The ligand was prepared in two steps. In the first step a solution of salicylaldehyed in methanol reacted under reflux with hydrazinemonohydrate to give an intermediate compound which reacted in the second step with 2, 4, 6-trihydroxidernonohydrate giving the tientioned ligand. The complexes were synthesis by direct reaction of the corresponding metal chloride with ligand. The ligand and the complexes have been characterized by spectroscopic methods [" H NMR, IR, UV-Vis,, atomic absorption], HPLC microanalysis along with conductivity measurements. From the abo

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Publication Date
Sun Dec 31 2000
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
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Publication Date
Fri Jan 01 2021
Journal Name
International Journal Of Drug Delivery Technology
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Publication Date
Fri Jun 01 2012
Journal Name
Pharmacie Globale
Synthesis and microbiological study of new sulfonamides

In contrast to the classical antibacterial sulfa drugs that are unsubstituted or monosubstituted, our newly synthesized analogs were designed to obtain sulfonamide moiety containing disubstituted hetero nitrogen atom. These compounds were formed successfully by chlorosulfonation of acetanilide and the product was treated with different cyclic amines and finally amide hydrolysis was necessary to get agents that were analyzed for IR, UV, CHN, melting points and solubility. At last, we studied their antibacterial activity on certain types of bacteria and we noticed the inactivity due to possible steric factor. Principly, this means these products have no inhibiting action against the used microbes.

Publication Date
Wed Sep 12 2012
Journal Name
Journal Of Engineering
Design and Implementation of a Vlsm Simulator

Variable-Length Subnet Masks (VLSM), often referred to as "subnetting a subnet", is used to maximize addressing efficiency. The network administrator is able to use a long mask on networks with few hosts, and a short mask on subnets with many hosts. This addressing scheme allows growth and does not involve wasting addresses. VLSM gives a way of subnetting a network with minimal loses of IP addresses for a specific range. Unfortunately, the network administrator has to perform several mathematical steps (or use charts) to get the required results from VLSM. In this paper, a simple graph simulator is proposed (using Visual Basic 6.0 Language) to perform all the required mathematical steps and to display the obtained required information (the

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Publication Date
Sat Oct 19 2024
Journal Name
European Journal Of Human Genetics
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Publication Date
Tue Feb 12 2019
Journal Name
Iraqi Journal Of Physics
Calculated the diffuse and direct parts of global solar radiation in Baghdad city for the period (1983-2005) depending on clearness index by applying the two world models of Liu -Jordan

In this paper solar radiation was studied over a region of Baghdad (Latitude 33.3o and longitude 44.4o). The two parts of global solar radiation: diffuse and direct solar radiation were estimated depending on the clearance index of measured data (Average Monthly mean global solar radiation). Metrological data of measured (average monthly mean diffuse and direct solar radiation) were used to comparison the results and show the agreement between them. Results are determined by applying Liu and Jordan two models (1960). Excel 2007program is used in calculation, graphics and comparison the results.

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