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TP53 polymorphism in plasma cell myeloma.

Szymon Andrzej Zmorzynski1, Iwona Korszen-Pilecka, Magdalena Wojcierowska-Litwin

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Summary

The TP53 codon 72 polymorphism (P72R) is linked to a higher risk of plasma cell myeloma (PCM) and impacts patient survival. This genetic factor may influence bortezomib treatment outcomes in PCM patients.

Keywords:
TP53 geneapoptosisbortezomibnecrosisplasma cell myelomapolymorphism

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Area of Science:

  • Genetics
  • Oncology
  • Pharmacogenomics

Background:

  • Predictive factors for bortezomib treatment in plasma cell myeloma (PCM) are limited.
  • The TP53 codon 72 polymorphism (P72R) influences protein function and may play a role in cancer development and treatment response.

Purpose of the Study:

  • To investigate the association between TP53 P72R polymorphism and PCM risk.
  • To determine if P72R polymorphism affects overall survival (OS) in PCM patients.
  • To assess the impact of P72R polymorphism on bortezomib sensitivity in PCM cell cultures.

Main Methods:

  • TP53 P72R polymorphism was analyzed in 59 newly diagnosed PCM patients and 50 healthy controls using RFLP-PCR.
  • Chromosomal aberrations were detected by cIg-FISH.
  • Lymphocyte cell cultures from 40 PCM patients were treated with varying concentrations of bortezomib.

Main Results:

  • The P allele and PP/PR genotypes of P72R polymorphism were significantly more frequent in PCM patients compared to controls (p=0.02 and p=0.04, respectively).
  • The PP genotype was associated with higher necrosis rates at 2 nM bortezomib in cell cultures (p=0.006).
  • Patients with the PP genotype had a shorter OS (12 months) compared to PR/RR genotypes (20 months) (p=0.04).

Conclusions:

  • TP53 P72R polymorphism may be associated with increased PCM risk and altered overall survival.
  • The study found no consistent effect of P72R polymorphism on apoptosis and necrosis in bortezomib-treated PCM cell cultures.
  • Further research is needed to clarify the role of P72R polymorphism in bortezomib sensitivity.