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تقييم sFas ligand, sFas وcaspase - 3 في المرضى المصابين بمرض ابيضاض الدم النقياني المزمن == Assessment Of Soluble Fas, Soluble Fas Ligand And Caspase - 3 In Patients With Chronic Myeloid Leukemia
Author name:
سحر راضي ياسر
Supervisor name:
ميسون علي سليم | بسام فرنسيس متي
General topic:
Medicine
Specific topic:
Microbiology - Immunology
Degree:
Master
University:
Mustansiriyah University
Language:
English
University location:
Baghdad
First pages:
19T1138 - p.pdf
Abstract:
ابيضاض الدم النقياني المزمن هو اضطراب التكاثر النقي النسيلي للخلايا الجذعية ويتميز بواسطة فلادلفيا كروموسوم وهو انتقال متبادل بين كروموسوم 9 و22. الجين المسرطن المتحد الجديد المتولد على كروموسوم 22 كنتيجة للانتقال يسمى BCR - ABL gene. في اغلبية المرضى, هذ | Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the haemopoietic stem cell, defined by the Philadelphia chromosome (Ph) - reciprocal translocation between chromosomes 9 and 22. The novel fusion oncogenes generated on chromosome 22 as a result of this translocation are called BCR - ABL gene. In the majority of patients, this oncogene transcribes a 210 - kDa constitutively active protein tyrosine kinase, often referred to as p210BCR - ABL, which is necessary for the transformation of the disease. The introduction of tyrosine kinase inhibitor (TKI) - imatinib mesylate (IM) - marked a major advance in CML treatment in terms of efficacy and tolerability and has now become the first line of therapy. In CML, besides genetic change during which a normal cell is transformed into a malignant one, evasion of apoptosis (programm cell death PCD) is one of the essential changes in a cell that cause malignant transformation. So ‘Evading apoptosis’ has been recognized as one of the six hallmarks of cancers, as reduced apoptosis or its resistance plays a vital role in carcinogenesis. Soluble receptors (sFas) that act as decoys, binding FasL and preventing association with transmembrane Fas. So production of sFas in tumor patients may be a key mechanism to inhibit Fas - mediated apoptosis. Soluble FasL competes with the membrane - bound counterpart; however, it can act even as an antagonist preventing apoptosis induction by the membrane integrated form of the ligand. Recently, caspase - 3 has been demonstrated to play an important role in determining the cellular sensitivity to diverse apoptotic stimuli, also it is involved in a number of non - apoptotic events. So the aims of the study were to estimate the level of serum sFas, sFas ligand & caspase - 3 in patients with chronic myeloid leukemia at time of diagnosis (newly diagnosed), then after receiving imatinib myselate treatment with optimal response and compare them with healthy control. It was a prospective study, included 56 Iraqi CML patients (25 were males and 31 were females with Age ranged from 15 - 78 years) attending to Baghdad teaching hospital/hematology department between November 2012 up to June 2013, were categorized by fluorescence in situ hybridization analysis (FISH) for Ph chromosome into two stages, newly diagnosed CML patients (FISH Ph cells result ? 90% ) not received any treatment and optimally treated (complete cytogenetic response (CCgR) = FISH Ph cells result < 1% or by major molecular response (MMoR) = BCR - ABL : ABL ?0.10% by International Scale, on RT - Q - PCR) with imatinib mesylate 400 mg/day at least 1 year. Then used an ELISA technique to assess serum level of sFas, sFas Ligand (sFasL) & Caspase - 3 for each patients of CML, and compared them with 28 apparently healthy volunteers used as control. The controls were age and sex matched with the patients, they were not taken medication and with no history of chronic illness and/or acute infection. As well as, they were nonsmoker and nondrinker. For patients the inclusion criteria including all patients were free of fever and other chronic illness such as diabetes mellitus, hypertension and infection; also they had no history of smoking and drinking of alcohol. And the exclusion criteria including patients suffering from any chronic, debilitating disease and other blood disorders were not taken.The observed results revealed the following : ? Patients were included in the study, male : female ratio was 0.8 : 1with mean age 42.6± 14.0.? The mean± SD serum of sFas levels (pg/ml) for the newly diagnosed and optimally responded of CML was 1163.6±231.5 and 1021.7±360.6 respectively.? The mean± SD serum of sFas Ligand levels (pg/ml) for the newly diagnosed and optimally responded of CML was 216.9±165.7 and 147.7±91 respectively. ? The median serum of Caspase - 3 (ng/ml) for the newly diagnosed and optimally treated cases was 0.421 and 0.361 respectively. ? The mean± SD serum of sFas and sFas Ligand levels (pg/ml) for the healthy group was 970.1±361.7, 152.5±98 consequently. The median serum of Caspase - 3 (ng/ml) for the healthy group was 0.314.? Serum sFas level was increased in newly diagnosed compare with optimal responder and healthy control group. Also serum sFas level in optimal responder group was increase when compared with healthy control group. The differences observed were no statistical significance (P=0.09).? Serum sFasL level was increased in newly diagnosed patients of CML when compared with optimal responder and healthy control group. But serum sFasL level in optimal responder group was decreased when compared with healthy control group. The differences observed were non statistical significance (P=0.07).? Serum Caspase - 3 level showed statistically significant (P ?0.001) increase in newly diagnosed when compared with healthy control group. While it was in optimal responder group was statistically increased (not significant P=0.13) when compared with healthy control group. And its level was increased in newly diagnosed compare with responder group which was statistically significant (P= 0.04).Finally, this study concluded that increase in sFas and sFas Ligand &Caspase - 3 in newly diagnosed CML patients compared with optimally and healthy control groups. Also concluded that Caspase - 3 was a good confirmed test to diagnose newly CML cases
