【摘 要】
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Introduction:Chronic lymphocytic leukemia (CLL) is characterized by a high heterogeneity in disease progression and outcome.The strongest negative predictor
【机 构】
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UniversityHospitalSalzburgAustria
【出 处】
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中国上海第七届国际新药发明科技年会
论文部分内容阅读
Introduction:Chronic lymphocytic leukemia (CLL) is characterized by a high heterogeneity in disease progression and outcome.The strongest negative predictor is a deletion at the 17p13 locus affecting appr.7-12 % of all newly diagnosed CLL patients.This percentage increases to appr.40% in therapy refractory and heavily pretreated patients.It has been shown that del 17p 13,resulting in a functional p53 knockout,predisposes to therapy resistance in CLL.Recently we could show that arsenic trioxide (ATO),which is already used for treatment of APL,induces significantly higher apoptosis rates in B-CLL cells carrying a dell7pl3 as compared to B-CLL cells lacking this chromosomal aberration.Thus loss of p53 appears to sensitise B-CLL cells to ATO treatment.Methods:The impact of p53 on ATO-induced apoptosis was investigated using the p53 inhibitor Pifithrin-α,and in mouse embryo fibroblasts (MEFs) deficient for p53 or its downstream target p21.Apoptosis/Necrosis induction was assessed by FACS (Annexin V/7-AAD) or the cell metabolism-based XTT assay.
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