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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
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Efficacy, safety and Cardiovascular Disease Risk Lowering Ability of ACE Inhibitors, B-Blockers and Combination Antihypertensive Drug Regimes in Iraq
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Hypertension is a major health problem throughout the world because of its high prevalence and its association with increased risk of cardiovascular diseases. It is defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. The aim of this study was to compare the efficacy, safety and cardiovascular disease risk lowering ability, of three antihypertensive drug regimens.

A retrospective study was carried out on 66 hypertensive patients, divided in to three groups based on their antihypertensive drug regimens (ACE inhibitors, β-blockers treated and combination antihypertensive therapy, the combination therapy consist of two or more of the following antihypertensive drugs ACE inhibitor di

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Publication Date
Fri Jun 01 2018
Journal Name
J. Pharm. Sci. & Res
Periodontal health status for post-menopausal women with and without osteoporosis (Clinical and radiographical study)
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Publication Date
Thu Jul 31 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Salivary α-Amylase and Albumin Levels in Patients with Chronic Periodontitis and Poorly or Well Controlled Type II Diabetes Mellitus
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Background: Recent studies suggest that chronic periodontitis (CP) and type2 diabetes mellitus (T2DM) are bidirectionally associated. Analysis of saliva as a mirror of oral and systemic health could allow identification of α amylase (α-Am) and albumin (A1) antioxidant system markers to assist in the diagnosis and monitoring of both diseases. The present study aims at comparing the clinical periodontal parameters in chronic periodontitis patients with poorly or well controlled Type 2Diabetes Mellitus, salivary α-Am, A1, flow rate (FR) and pH then correlate between biochemical, physical and clinical periodontal parameters of each study and control groups. Materials and Methods: 80 males, with an age range of (35-50) years were divide

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Publication Date
Thu Oct 03 2013
Journal Name
J. Of University Of Anbar For Pure Science
Determination of thyroid hormone levels in the serum of Non- dialyzed patients with chronic renal failure
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Thyroid hormones, triiodothyronine (T3) and thyroxin (T4) play an important role in growth, development, and physiology of the kidney. The kidney has a central role in metabolism and clearance of these hormones as well as thyroid – stimulating hormone (TSH). Chronic renal failure (CRF) is a state of irreversible deceleration in renal function results in alterations in internal milieu, which affects the synthesis and secretory rate of hormones. To evaluate the thyroid hormone levels in non-dialyzed patients with chronic renal failure (CRF); 24 patients with CRF aged 30-70 years, mean±S.d. (48.458 ± 13.569) and 48 healthy volunteers who served as controls aged 30-70 years (43.104 ± 12.387) were studied for their thyroid function status u

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Publication Date
Mon Jan 01 2018
Journal Name
Journal Of Pharmacy Research
Pulsatile drug delivery system - A review article
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Publication Date
Sat Dec 31 2022
Journal Name
International Journal Of Dentistry
Bond Strength Survival of a Novel Calcium Phosphate-Enriched Orthodontic Self-Etching System after Various Ageing Protocols: An In Vitro Study
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Objective. This study aimed to evaluate the orthodontic bond strength and enamel-preserving ability of a hydroxyapatite nanoparticles-containingself-etch system following exposure to various ageing methods. Materials and Methods. Hydroxyapatite nanoparticles (nHAp) were incorporated into an orthodontic self-etch primer (SEP, Transbond™ plus) in three different concentrations (5%, 7%, and 9% wt) and tested versus the plain SEP (control) for shear bond strength (SBS), adhesive remnant index (ARI) scores, and enamel damage in range-finding experiments using premolar teeth. The best-performing formulation was further exposed to the following four artificial ageing methods: initial debonding, 24 h water storage, one-month water stora

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Treatment of polycyclic armoatic hydrocarbone in agriculture
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Despite the multiple sources of polycyclic compounds in the agricultural environment, this study suggests that it is possible to adopt the events of plants and their associated microorganisms in the soil, such as mushrooms and bacteria in the decomposition of these compounds can also use harvested plants such as barley and alfalfa grown for animal feed

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Publication Date
Fri Jan 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
DYNAMIC MODELING FOR DISCRETE SURVIVAL DATA BY USING ARTIFICIAL NEURAL NETWORKS AND ITERATIVELY WEIGHTED KALMAN FILTER SMOOTHING WITH COMPARISON
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Survival analysis is widely applied in data describing for the life time of item until the occurrence of an event of interest such as death or another event of understudy . The purpose of this paper is to use the dynamic approach in the deep learning neural network method, where in this method a dynamic neural network that suits the nature of discrete survival data and time varying effect. This neural network is based on the Levenberg-Marquardt (L-M) algorithm in training, and the method is called Proposed Dynamic Artificial Neural Network (PDANN). Then a comparison was made with another method that depends entirely on the Bayes methodology is called Maximum A Posterior (MAP) method. This method was carried out using numerical algorithms re

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Publication Date
Wed Dec 30 2015
Journal Name
College Of Islamic Sciences
Living Dengue (Cause and treatment)
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This research dealt with the modern dengue living in its linguistic meaning and where this dengue will be, and its cause and treatment, then concluded the talk about the search with the results envisaged from this research, has been shown that the main reason in living dengue: is after the slave of the book of God and the Sunnah of the Prophet peace be upon him Him.

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Publication Date
Thu Jun 30 2022
Journal Name
Journal Of Economics And Administrative Sciences
Estimation of Time of Survival Rate by Using Clayton Function for the Exponential Distribution with Practical Application
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Each phenomenon contains several variables. Studying these variables, we find mathematical formula to get the joint distribution and the copula that are a useful and good tool to find the amount of correlation, where the survival function was used to measure the relationship of age with the level of cretonne in the remaining blood of the person. The Spss program was also used to extract the influencing variables from a group of variables using factor analysis and then using the Clayton copula function that is used to find the shared binary distributions using multivariate distributions, where the bivariate distribution was calculated, and then the survival function value was calculated for a sample size (50) drawn from Yarmouk Ho

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