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In B-CLL, the codon 72 polymorphic variants of p53 are not related to drug resistance and disease prognosis

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Item Type:Article
Title:In B-CLL, the codon 72 polymorphic variants of p53 are not related to drug resistance and disease prognosis
Creators Name:Sturm, I. and Bosanquet, A.G. and Hummel, M. and Doerken, B. and Daniel, P.T.
Abstract:BACKGROUND: A common sequence polymorphism at codon 72 of the p53 gene encoding either arginine or proline was recently shown to be functionally relevant for apoptosis induction in vitro. In B-type chronic lymphocytic leukemia (B-CLL), p53 gene mutations occur in a subset of patients and are associated with impaired survival and drug resistance. Here, we address the functional relevance of the codon 72 single nucleotide (SNP) polymorphism for cell death sensitivity following exposure to clinically employed cytotoxic drugs and gamma-irradiation. METHODS: 138 B-CLL samples were analysed by SSCP-PCR and sequencing for single nucleotide polymorphism at codon 72 of the p53 gene. The in vitro cytotoxicity assay (DiSC-assay) was performed with 7 drugs (chlorambucil, mafosfamide, fludarabine phosphate, methylprednisolone, doxorubicin, vincristine) or gamma-irradiation. RESULTS: Of the 138 B-CLL samples, 9 samples were homozygous for proline (Pro/Pro), 78 samples homozygous for arginine (Arg/Arg), and 49 samples heterozygous (Arg/Pro). No differences were found for patient survival and cell death triggered by 7 cytotoxic drugs or gamma-irradiation. CONCLUSION: These data indicate that polymorphic variants of p53 codon 72 are not clinically relevant for apoptosis induction or patient survival in B-CLL.
Keywords:Antineoplastic Agents, Apoptosis, Arginine, Chlorambucil, Codon, Cyclophosphamide, DNA Mutational Analysis, Doxorubicin, Neoplasm Drug Resistance, Gamma Rays, Neoplastic Gene Expression Regulation, p53 Genes, Homozygote, B-Cell Chronic Lymphocytic Leukemia, Methylprednisolone, Mutatio
Source:BMC Cancer
Publisher:BioMed Central
Page Range:105
Date:18 August 2005
Official Publication:https://doi.org/10.1186/1471-2407-5-105
PubMed:View item in PubMed

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