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


CONCLUSIONS
These data indicate that polymorphic variants of p53 codon 72 are not clinically relevant for apoptosis induction or patient survival in B-CLL.
Sturm
Isrid
I
Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charité, Campus Berlin-Buch, Berlin, Germany. isrid.sturm@charite.de
Bosanquet
Andrew G
AG
Hummel
Michael
M
Dörken
Bernd
B
Daniel
Peter T
PT
D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001120:Arginine / Q000235:genetics; D002699:Chlorambucil / Q000494:pharmacology; D003062:Codon; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006720:Homozygote; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011392:Proline / Q000235:genetics; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D003062:Codon; D001084:Vidarabine Phosphate; D002699:Chlorambucil; C042382:fludarabine phosphate; C048341:mafosfamide; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D001120:Arginine; D011392:Proline; D008775:Methylprednisolone