Detection of p53 dysfunction by flow cytometry in chronic lymphocytic leukaemia.
In chronic lymphocytic leukaemia (CLL) cells, functional impairment of the p53 pathway is detectable by Western blotting as impaired up-regulation of p21 (a transcriptional target of p53) in response to ionizing radiation (IR). The type A defect is characterized by baseline p53 overexpression and is associated with TP53 mutation. The type B defect is characterized by impaired IR-induced p53 up-regulation and is associated with inactivation of the ataxia telangiectasia-mutated gene (ATM). Both abnormalities are strongly associated with adverse clinical outcome. In the present study, flow cytometry was found to be an effective alternative to Western blotting in the detection of p53 dysfunction in CLL.
Carter
A
A
Department of Haematology, Royal Liverpool University Hospital, Liverpool L7 8XP, UK.
Lin
K
K
Sherrington
P D
PD
Pettitt
A R
AR
D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005434:Flow Cytometry / Q000379:methods*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53