P73 status in B-cell chronic lymphocytic leukaemia.
B-cell chronic lymphocytic leukemia is a heterogenous disease with disturbed apoptosis in which the precise molecular defects leading to this pathogenesis are still unclear. The p73 gene (a p53 homologue) encodes 2 proteins with opposing functions. TAp73 induces cell cycle arrest and apoptosis, whilst the oncogenic deltaNp73 inhibits both TAp73 and p53 induced apoptosis. Microsatellite analysis was performed to investigate the p73 gene locus in B-CLL. Moreover, we investigated the expression of the TAp73 and deltaNp73 variant by measuring the mRNA transcripts in 51 B-CLL patients by real-time RT-PCR. And in addition, protein expression was analyzed by Western blotting technique in 20 B-CLL patients. There was no evidence of clonal loss of heterozygosity at 1p36, the p73 gene locus in B-CLL patients. The real time RT-PCR analysis showed that the expression of both p73 gene variants was much higher in leukemic cells compared to controls. In 17/20 (85%) patients deltaNp73 and TAp73 protein were present. The observed increase of expression of the antiapoptotic deltaNp73 variant in neoplastic cells may lead to a functional p53 inactivation. This mechanism might be relevant in malignancies with an intact p53 gene but disturbed apoptosis mechanisms such as in B-CLL.
Leupin
Nicolas
N
Department of Clinical Research, Medical Oncology/Hematology, University and Inselspital Bern, Switzerland.
Lüthi
Alexander
A
Novak
Urban
U
Grob
Tobias J
TJ
Hügli
Barbara
B
Graber
Hans
H
Fey
Martin F
MF
Tobler
Andreas
A
D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human