p53 protein expression in chronic lymphocytic leukemia.
Alterations in the function of the p53 pathway are frequently described in chronic lymphocytic leukemia (CLL), mostly associated with deletion of 17p13 and/or mutations of the TP53 gene. In the present study, we investigated 103 CLLs for the impact of protein expression of full-length p53 and its isoforms β and γ. A strong correlation between deletions of 17p13 and an accumulation of full-length p53 protein was found and was associated with a worse outcome compared to CLL with normal p53 (treatment-free survival p < 0.001, overall survival p = 0.04). Interestingly, the relative expression levels between full-length p53 protein and its isoforms β and γ were significantly altered in CLL even without deletions of 17p13, compared to normal B-cells (p = 0.005). Furthermore, CLLs with higher p53 protein ratios showed worse clinical courses compared to CLLs with lower p53 protein ratios. Taken together, the differential expression of p53 isoforms could disrupt the p53 response and contribute to CLL pathogenesis.
Department of Hematology, Medical Faculty, University of Duisburg-Essen, Essen, Germany. ludger.sellmann@uk-essen.de
Ludger
L
Sellmann
Alexander
A
Carpinteiro
Holger
H
Nückel
René
R
Scholtysik
Dörte
D
Siemer
Ludger
L
Klein-Hipass
Dieter
D
Kube
Jan
J
Dürig
Ulrich
U
Dührsen
Jens
J
Stanelle
Ralf
R
Küppers
D015153:Blotting, Western; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53