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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
Mon Jul 01 2013
Journal Name
Political Sciences Journal
Towards Promoting Political Participation of Female - University Students - Field Study on Al-Quds Open University Female - Students - Rafah
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نحو تعزيز المشاركة السياسية للطالبات الجامعيات الفلسطينيات

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Publication Date
Fri Jun 30 2023
Journal Name
Iraqi National Journal Of Nursing Specialties
Effectiveness of Intervention Program on Nurses' Practices concerning Diet Instructions for Orthopedic Patients treated by Internal Fixation Devices
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Abstract

Objective(s): To determine the interventional program effectiveness on nurses' practices concerning diet instructions for orthopedic patients treated by internal fixation devices.

Methodology: A quantitative approach using prexperimental design is conducted to determine the effectiveness of an interventional program on nurses’ practices regarding orthopedic patients diet instruction and teaching after internal fixation implemented. The study has started from 1st of April 2022 and ended on 15th of December, 2022. The conduction of the study in Misan governorate  / Al-Zaharawy surgical hospital. A non-probability, purpo

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Publication Date
Sun Oct 15 2017
Journal Name
Research Journal Of Applied Sciences, Engineering And Technology
Optimization of IPv6 Protocol Independent Multicast-Sparse Mode Multicast Routing Protocol based on Greedy Rendezvous Point Selection Algorithm
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Publication Date
Mon Feb 01 2021
Journal Name
Engenharia Agrícola
HYPERSPECTRAL SPECTROSCOPY TO DETECT DIFFERENT RESPONSES OF TWO SOYBEAN (GLYCINE MAX) CULTIVARS TO CHARCOAL ROT (MACROPHOMINA PHASEOLINA) TOXIN
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Publication Date
Wed Jan 01 2020
Journal Name
Journal Of Biotech Research
Bacteriocin Production by Staphylococcus Epidermidis the Normal Flora of Outer Ear: A Potential Probiotic Against Outer Ear Infections
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Publication Date
Sun Mar 01 2015
Journal Name
Current Research In Microbiology And Biotechnology
Evaluation for the Cytotoxic Effect of Exotoxin A Produced by Pseudomonas aeruginosa on Mice by using Cytogenetic Parameters
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This research was conduct to evaluate the cytotoxic effect of exotoxin A (ETA) produced by Pseudomonas aeruginosa on mice in comparison with (phosphate buffer saline (PBS) as a negative control. The effect of the toxin was measured by employing the cytogenetic analysis which included (the mitotic index (MI), chromosomal aberrations (CAs), micronucleus (MN) and sperm abnormalities) parameters. In order to specify the cytotoxic effect of the toxin, three doses of ETA (125, 250 and 500 ng/ml) were used. Results showed that ETA was found to cause a significant decrease in mitotic index (MI) percentage, while significant increase in micronucleus (MN), chromosomal aberrations (CAs) and sperm abnormalities parameters in compression with control wa

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Publication Date
Sun Jan 01 2023
Journal Name
Technologies And Materials For Renewable Energy, Environment And Sustainability: Tmrees22fr
Theoretical insights into the study of the electronic transition reaction process from D35CPDT molecule dye to SnO2 semiconductor
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Publication Date
Sun Nov 02 2025
Journal Name
Kufa Journal Of Arts
Compound thought :Or face crises from oneself to politics A Philosophical Study on the Editions of Edgar Moran
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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
A Comparison of Parameters Estimation Methods for the Negative Binomial Regression Model under Multicollinearity Problem by Using Simulation
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This study discussed a biased estimator of the Negative Binomial Regression model known as (Liu Estimator), This estimate was used to reduce variance and overcome the problem Multicollinearity between explanatory variables, Some estimates were used such as Ridge Regression and Maximum Likelihood Estimators, This research aims at the theoretical comparisons between the new estimator (Liu Estimator) and the estimators

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Synthesis of New Heterocyclic Derivatives from 4-(3, 5-Dimethyl-1-phenyl-1H-pyrazol-4-ylazo)- benzoic acid
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In this work pyrazolin derivatives were prepared from the diazonium chloride salt of 4-aminobenzoic acid. Azo compounds were prepared from the reaction of an ethanolic solution of sodium acetate and calculated amount of active methylene compound namely, acetyl acetone to obtain the corresponding hydrazono derivative (1). Cyclocondensation reaction of compounds (1) with hydrazine hydrate and phenyl hydrazine in boiling ethanol affording the corresponding pyrazoline-5-one derivatives of 4-aminobenzoic acid (2,3). Then compound (3) was reacted with thionyl chloride to give the corresponding acid chloride derivative(4), followed by conversion into the corresponding acid hydrazide derivative (5) carboxylic acid thiosemicarbazide (11), esters

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