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العنوان
Assessment of caspase-­2 activity in patients with acute leukemia /
المؤلف
Elzehery, Rasha Rizk Abass.
هيئة الاعداد
باحث / رشا رزق عباس الزهيري
مشرف / سامح سيد احمد شمعة
مشرف / دعاء عبدالله العدل
مشرف / عزة عبدالباقي البيومي
مناقش / لطفى عبدالنبى
الموضوع
Leukemia - Chemotherapy. Immunotherapy. tineoplastic agents. Leukemia - Immunological aspects.
تاريخ النشر
2005.
عدد الصفحات
134 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب
تاريخ الإجازة
1/1/2005
مكان الإجازة
جامعة المنصورة - كلية الطب - الباثولوجيا الإكلينيكية
الفهرس
Only 14 pages are availabe for public view

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from 147

Abstract

Numerous studies have indicated that the growth, differentiation, and survival of acute leukemia cells are regulated by intracellular and extracellular signals. Most signals that lead to apoptosis do so by activating intrleukin­1 beta converting enzyme like proteases termed caspase. Caspase­2 is an intracellular cysteine protease that exists as proenzyme (inactive), becoming activated during the cascade of events associated with apoptosis. Caspase­2 mRNA can be spliced into two isoforms: the long form is pro­apoptotic while the short form is anti­apoptotic This study aims: to determine the caspase­2 activity in a number of patients with acute leukemia at diagnosis and correlate its proteolytic activity with clinical outcome and other laboratory variables. The present study comprised 36 leukemic patients besides 14 apparently healthy individuals as a control group. The patients were categorized as follows::group I: 13 patients with AML (7 males and 6 females, mean age: 42.2 (R+ (B18.6 years), group II: 15 patients with ALL (11 males and 4 females, mean age: 25.7 (R+ (B15.4 years) and group III: 8 patients with CML in blastic crisis (4 males and 4 females, mean age: 37.6 (R+ (B13.5 years). The results of this study could be summarized as follows: Caspase­2 activity (before and after induction of apoptosis) was statistically and significantly lower in all patient groups when compared to controls. A significant difference in caspase­2 activity was elicited among different FAB subtypes in both AML and ALL.. Patients with CML in blastic phase elicited a non­significant correlation between caspase­2 activity in induced cells and all studied parameters. Conclusion: Caspase­2 activity is low in patients with acute leukemia, suggesting that failure of apoptosis could be attributed to dysregulation of caspase activation pathways in leukemic patients. Caspase­2 pathway dysregulation has a minor role in patients with CML in blastic crisis. Better outcome is associated with a higher activity of caspase­2, suggesting that regardless of the upstream events that modulate the caspase pathways, caspase­2 could be used as a predictor of achieving CR in acute leukemia. Fold increase of caspase­2 activity above a critical threshold is strikingly related to the probability of achieving CR in patients with acute leukemia.