title: Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: University and Inselspital, Department of Clinical Research, Medical Oncology/Haematology, Berne, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Novak
authors.forename: T J
authors.initials: TJ
authors.lastname: Grob
authors.forename: G
authors.initials: G
authors.lastname: Baskaynak
authors.forename: U R
authors.initials: UR
authors.lastname: Peters
authors.forename: S
authors.initials: S
authors.lastname: Aebi
authors.forename: D
authors.initials: D
authors.lastname: Zwahlen
authors.forename: M P
authors.initials: MP
authors.lastname: Tschan
authors.forename: K A
authors.initials: KA
authors.lastname: Kreuzer
authors.forename: E O
authors.initials: EO
authors.lastname: Leibundgut
authors.forename: J F
authors.initials: JF
authors.lastname: Cajot
authors.forename: A
authors.initials: A
authors.lastname: Tobler
authors.forename: M F
authors.initials: MF
authors.lastname: Fey
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins