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

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 γ-irradiation.Of the138 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 γ-irradiation.These data indicate that polymorphic variants of p53 codon 72 are not clinically relevant for apoptosis induction or patient survival in B-CLL.The tumor suppressor gene p53 plays a central role in the induction of cell cycle arrest, senescence and apoptosis [1-5]. The polyproline domain (PP domain) of p53 spanning amino acids 62–91 is involved in apoptosis induction and facilitates transactivation of pro-apoptotic genes by p53 [6].Located in this PP domain is at codon 72 a common single nucleotide polymorphism (SNP), resulting in either a proline residue (p53Pro) or an arginine residue (p53Arg). Thus, each individual inherits a p53 genotype that can be heterozygous (Arg/Pro) or homozygous for either arginine (Arg/Arg) or proline (Pro/Pro). The polymorphism is balanced, varies with latitude and race, and is maintained at different allelic frequencies across the population [7]. These two SNPs appear to be different both biochemically and biologically [8-11]. Differences in apoptosis susceptibility to cytotoxic drugs were described [12,13], and the response and survival to radiochemotherapy in clinical samples of squamous cell carcinomas was found to be increased in case the arginine allele is retained [13].Chronic lymphocytic B-cell lymphoma is still an incurable disease and may be addressed as a disease of intrinsic apoptosis deficiency. It is a disease where the mutational status of the p53 gene is