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العنوان
flt3 gene mutation and stat5 protein activation in egyptian acute myeloid leukemia patients/
المؤلف
Kamel, Yasmine Mahmoud Nabil Mohamed.
هيئة الاعداد
باحث / ياسمين محمود نبيل محمد كامل
مناقش / فتحى محمد طاش
مناقش / سامي حسين جلال
مناقش / نادية أحمد فوزى برغش
الموضوع
Biochemistry.
تاريخ النشر
2012.
عدد الصفحات
P71. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الكيمياء الحيوية (الطبية)
تاريخ الإجازة
13/5/2012
مكان الإجازة
جامعة الاسكندريه - كلية الطب - الكيمياء الحيوية
الفهرس
Only 14 pages are availabe for public view

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Abstract

Acute myeloid leukemia is a clonal hematopoietic disorder that is frequently associated with genetic instability characterized by a diversity of chromosomal and molecular changes.
One of the most common mutations in AML are DNA duplications in the FLT3 gene. FLT3 mutations result in downstream activation of a number of signaling pathways, of these, the STAT5 pathway appears to be most differentially regulated in FLT3-ITD cells compared to FLT3-WT cells.
The aim of the present work was to determine the frequency of FLT3 mutation among AML patients, to assess STAT5 phosphorylation among AML patients and to evaluate the relation between FLT3 mutation, STAT5 phosphorylation and treatment outcome in these patients.
In order to achieve these goals, this study included 50 newly diagnosed AML patients and 30 age and sex matched healthy adult volunteers.
Following proper selection of patients and control subjects, the following laboratory tests were performed:
1- PCR to detect the presence of FLT3-ITD mutation.
2- Western blotting to assess the degree of STAT5 phosphoylation.
After recovery from chemotherapy induced BM aplasia, patients were reevaluated as regards clinical picture and bone marrow aspirate to determine their response to induction chemotherapy. Also, the degree of STAT5 phosphorylation was reassessed by western blotting.
The following results were obtained:
1- FLT3-ITD mutation was detected in 50% of AML patients, and in none of the control subjects.
2- The highest frequency of FLT3-ITD cases was in M3 class and in the t(15;17) group.
3- The age in AML patients with FLT3-ITD was significantly higher than those with FLT3-WT.
4- No significant difference was observed between AML patients with FLT3-ITD and those with FLT3-WT as regards sex, TLC, BM blast% or response to induction chemotherapy.
5- In AML patients with normal cytogenetics, no significant difference was observed between AML patients with FLT3-ITD and those with FLT3-WT as regards response to induction chemotherapy, however it greatly approached the significant level.
6- P-STAT5 levels were significantly higher in AML patients than control subjects.
7- On calculating the cut-off value, STAT5 was detected to be highly phosphorylated in 72% of AML patients.
8- No significant difference was observed between FLT3-WT and ITD groups as regards the level of P-STAT5 either before or after chemotherapy.
9- There was a signifi