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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
Fri Dec 24 2021
Journal Name
Oncology And Radiotherapy
The effect of different clinicopathological parameters on disease free survival in triple negative breast cancer Iraqi women
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Publication Date
Mon Mar 01 2021
Journal Name
Iraqi Journal Of Agricultural Sciences
CORRELATION STUDY BETWEEN THREE DIFFERENT GENES EXPRESSION AND CHRONIC MYELOID LEUKEMIA IN IRAQ
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The following study was conducted to investigate the correlation between the expression of three different genes (NOB1, DDX47, CD101( with the occurrence and development of chronic myeloid leukemia (CML) in Iraq. The difference in the expression of these genes between patients and healthy controls was studied. Moreover the correlation of age and gender with CML occurrence and comparing with control was also examined. Results showed significant increases in mean of gene expression level (ΔCt) of patient groups for all genes compared to the corresponding ΔCt means in control group, also the gene expression folding (2-ΔΔCt) reflect significant differences in the expression of these genes and CD101, mRNA showed the highest level in CML pati

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Free Fatty Acids and Biochemical Changes in Iraqi patients with Chronic Renal Failure
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Chronic renal failure (CRF) is progressive irreversible destruction of kidney tissue by disease which, if not treated by dialysis or transplant, will result in patient's death. This study was carried out on 30 patients (17 male and 13 female) with chronic renal failure. The aim of this research was studied the changes in the level of total protein ,albumin, calcium ,ionized calcium, phosphorous , iron ,ALP, LDH ,CK and FFA in patients with CRF before and after hemodialysis .The obtained results have been compared with 30 healthy subjects as control group (18male and 12 female). The results showed that there was significant increase in the level of calcium ,ionized calcium, phosphorous ,iron ,ALP,LDH,CK and FFA ,while there was a signifi

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Publication Date
Thu Jan 08 2026
Journal Name
Iraqi Journal Of Science
Effect of Diode Laser (805) nm on alpha-toxin production and antibiotic sensitivity of Staphylococcus aureus
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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Changes in the serum level of the trace elements in chronic renal
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Were studied changes in the concentration of copper, iron and zinc in blood serum of one hundred patients with chronic kidney and treated dialysis blood were also measured the level of calcium kidney and phosphate Calciotropic in serum of these patients took samples of blood from these patients before and after treatment dialysis vessels as well as the statement of changes in those standards Alkimaahiatih Results were compared with twenty-five healthy people (control group)

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Publication Date
Wed Jul 01 2020
Journal Name
Medico-legal Update
Evaluation of technical quality and procedural errors of root canal treatment performed by undergraduate and postgraduate dental students: A retrospective radiographic analysis
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Publication Date
Sat Feb 01 2014
Journal Name
World Journal Of Pharmaceutical Sciences
Detection of JAK2V617F Mutation and Serum Levels of Alkaline Phosphatase and Lactate Dehydrogenase in Chronic Myelogenous Leukemia.
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Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm arises from Bcr-Abl gene translocation (called Ph chromosome) in hematopoietic stem cells (HSCs). This genetic abnormality results in constitutive activation of tyrosine kinase and subsequent uncontrol growth and multiplication of granulocytes. The cornerstone in treatment of CML are tyrosine kinase inhibitors, of which imatinib is the most effectively used. JAK2V617F mutation is an acquired single nucleotide polymorphism (SNP) occurs in JAK2 gene and is associated with many hematological malignancy other than CML. It was thought that the two genetic abnormalities (Bcr-Abl and JAK2V617F) occur mutually; however, growing body of evidences suggested the reverse. This study a

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Publication Date
Mon Mar 01 2021
Journal Name
Journal Of Physics: Conference Series
Evaluation of total oxidant status and antioxidant capacity in sera of acute-and chronic-renal failure patients
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Abstract<p>Renal failure is a disease of the kidney, in which the renal excretory function is failed to process due to depression of the GFR. Renal failure is divided into acute and chronic depending on the period of the disease. The study was designed to investigate the level of oxidative stress in RF patients. Seventy-five subjects had enrolled in the study, who divided into three groups equally, in which they are healthy control, ARF patients, and CRF patients. The results had shown a significant <italic>(P<0.01)</italic> increase in the level of TOS for RF patients when compared with control. Also, a significant difference in the level of TOS has been observed between ARF and CR</p> ... Show More
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Publication Date
Mon Dec 04 2017
Journal Name
Al-qadisiyah Journal For Administrative And Economic Sciences
Survival Function Estimating of Single age Groups for Generalized Gamma Distribution with Simulation.
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The analysis of survival and reliability considered of topics and methods of vital statistics at the present time because of their importance in the various demographical, medical, industrial and engineering fields. This research focused generate random data for samples from the probability distribution Generalized Gamma: GG, known as: "Inverse Transformation" Method: ITM, which includes the distribution cycle integration function incomplete Gamma integration making it more difficult classical estimation so will be the need to illustration to the method of numerical approximation and then appreciation of the function of survival function. It was estimated survival function by simulation the way "Monte Carlo". The Entropy method used for the

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Publication Date
Sat Dec 01 2012
Journal Name
Journal Of Economics And Administrative Sciences
A comparison Some of Methods for Estimating Survival Function for Truncated Exponential Distribution
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Exponential distribution is one of most common distributions in studies and scientific researches with wide application in the fields of reliability, engineering and in analyzing survival function therefore the researcher has carried on extended studies in the characteristics of this distribution.

In this research, estimation of survival function for truncated exponential distribution in the maximum likelihood  methods and Bayes first and second method, least square method and Jackknife dependent in the first place on the maximum likelihood method, then on Bayes first method then comparing then using simulation, thus to accomplish this task, different size samples have been adopted by the searcher us

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