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دراسة جزيئية للطفرتين NPM1 - A وFLT3 - ITD مع التعبير النسخي للمورث الجزيئي FLT3 في نموذج من المرضى العراقيين البالغين المصابين بابيضاض الدم النقياني الحاد وعلاقتهما مع المؤشرات السريرية والمختبرية == Molecular Study of NPM1 - A, FLT3 - ITD Mutations and FLT3 Transcript Expression in a Sample of Iraqi Adult Acute Myeloid Leukemia Patients : Their Correlations with Clinicopathological Parameters
Author name:
شيماء محمد عبد اللطيف
Supervisor name:
ختام رزاق كاظم الخفاجي | علي محمد جواد
General topic:
Medicine
Specific topic:
Diseases - Blood
Degree:
Doctorate
University:
University of Baghdad - Faculty Of Medicine
Language:
English
University location:
Baghdad
First pages:
19T1546 - p.pdf
Abstract:
Acute myeloid leukemia is a hematological malignancy of myeloid progenitor cells characterized by anomalous proliferation, inhibition of differentiation and extension of leukemic cells blocked at the early stage of hematopoiesis. It has a great variability in the pathogenesis, clinical features, and treatment outcomes. Detection of molecular markers has become a smart tool to further division of patients in acute myeloid leukemia subgroups.Nucleophosmin1 mutations are found in approximately 30% of adult acute myeloid leukemia patients and are associated with a good outcome when detected in absence of duplications in the Fms - like tyrosine kinase 3 gene. Over 50 molecular Nucleophosmin1 mutation variants have been recognized; the most common one is Nucleophosmin1 - A mutation.The Fms - like tyrosine kinase 3 receptor is expressed on the surface of hematopoietic stem cells and plays a vital role in normal hematopoiesis. Numerous studies have revealed that high levels of Fms - like tyrosine kinase 3 were expressed in patients with acute myeloid leukemia. Fms - like tyrosine kinase 3 - Internal tandem duplication mutations are found in around 20 - 25% of patients with acute myeloid leukemia and are associated with increased transcript level of Fms - like tyrosine kinase 3 and with a poor scenario in adult acute myeloid leukemia patients.Aim of the Study1. Detect the frequency of Nucleophosmin1 - A; Fms - like tyrosine kinase 3 - Internal tandem duplication along with assessment of Fms - like tyrosine kinase 3 transcript expression in a sample of newly diagnosed Iraqi adult acute myeloid leukemia patients.2. Study the relationship of Nucleophosmin1 - A, Fms - like tyrosine kinase 3 - Internal tandem duplication mutations and Fms - like tyrosine kinase 3VItranscript expression with various clinicopathological parameters and French - American - British subtypes of the disease as well as the correlation among the three markers.Materials and MethodsThis is a cross - sectional study, conducted during the period extending between April 2015 and September 2016. The bone marrow aspirate samples of 53 adult acute myeloid leukemia patients were collected at the time of diagnosis and prior to treatment at the Hematology Ward of Baghdad Teaching Hospital in Medical City compared with 53 control individuals. All the control bone marrows obtained from patients with anemia and idiopathic thrombocytopenic purpura and were negative for infiltrative lesions. The related clinical and laboratory data for each patient were registered at the time of diagnosis.The study was conducted at Main Laboratory of Baghdad Teaching Hospital/ Medical City, Clinical and Communicable Diseases Research Center/College of Medicine/ University of Baghdad and Postgraduate Laboratory of Pathology and FoThe RNA was extracted and was reverse transcribed into cDNA. Real time polymerase chain reaction technique was applied on bone marrow aspirate samples of acute myeloid leukemia and control groups to detect the frequency of Nucleophosmin1 - A mutation, Fms - like tyrosine kinase 3 expression using a TaqMan probe and SYBR green assays respectively and detection of Fms - like tyrosine kinase 3 - Internal tandem duplication mutation using gel electrophoresis post polymerase chain reaction procedure
