Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia.
The p73 protein shares structural and functional similarities with the tumour-suppressor p53, but its role in neoplastic transformation is unknown. Alternative splicing leads to the expression of at least nine p73 C-terminal mRNA splice variants (alpha, beta, gamma, delta, epsilon, zeta, eta, eta1, theta). In this survey, we analyse the expression of p73 by real-time quantitative RT-PCR, its known C-terminal variants with an RT-PCR-Southern technique and by Western blot in samples of 51 patients with B-CLL, normal B lymphocytes from eight individuals, and five haematopoetic cell lines. p73alpha protein expression positively correlated with higher risk B-CLL stages (P = 0.046). Total p73 mRNA expression was higher (P = 0.01) and p73alpha protein more frequently detected (P = 0.008) in B-CLL compared with normal CD19+-B-lymphocytes. p73 C-terminal mRNA variants were expressed both in B-CLL and in normal B-lymphocytes, but their expression was biased since the gamma (P = 0.041), the theta (P < 0.001), and the eta variant (P = 0.033) prevailed in normal B-lymphocytes. In summary, we conclude that the accumulation of p73, the expression pattern of particular p73 variants and its link to progression may play a distinct role in the molecular pathology B-CLL.
Novak
U
U
University and Inselspital, Department of Clinical Research, Medical Oncology/Haematology, Berne, Switzerland.
Grob
T J
TJ
Baskaynak
G
G
Peters
U R
UR
Aebi
S
S
Zwahlen
D
D
Tschan
M P
MP
Kreuzer
K A
KA
Leibundgut
E O
EO
Cajot
J F
JF
Tobler
A
A
Fey
M F
MF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins