open access

Vol 55, No 4 (2017)
Original paper
Submitted: 2017-03-24
Accepted: 2017-12-18
Published online: 2018-01-04
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TP53 polymorphism in plasma cell myeloma

Szymon Andrzej Zmorzynski1, Iwona Korszen-Pilecka, Magdalena Wojcierowska-Litwin, Barbara Kwiatkowska-Drabik, Malgorzata Luterek, Sylwia Chocholska, Dorota Koczkodaj, Sylwia Popek, Malgorzata Michalak-Wojnowska, Grazyna Swiderska-Kolacz, Joanna Januszewska, Iwona Surowiec, Waldemar Tomczak, Marek Hus, Anna Dmoszynska, Marcin Pasiarski, Katarzyna Poniewierska-Jasak, Katarzyna Cieplinska, Olga Jankowska-Lecka, Agata Anna Filip
DOI: 10.5603/FHC.a2017.0022
·
Pubmed: 29333597
·
Folia Histochem Cytobiol 2017;55(4):203-211.
Affiliations
  1. Department of Cancer Genetics with Cytogenetic Laboratory, Medical University of Lublin, Poland

open access

Vol 55, No 4 (2017)
ORIGINAL PAPERS
Submitted: 2017-03-24
Accepted: 2017-12-18
Published online: 2018-01-04

Abstract

Introduction. Significant and accessible predictive factors for bortezomib treatment in plasma cell myeloma (PCM) are still lacking. TP53 codon 72 polymorphism (P72R) results in proline (P) or arginine (R) at 72 amino acid position, which causes synthesis of proteins with distinct functions. The aims of our study were to: 1) analyze whether this polymorphism is associated with an increased risk of PCM; 2) study whether the P72R polymorphism affects overall survival (OS) among PCM patients; 3) assess the possible association of the P72R polymorphism with sensitivity to bortezomib in cell cultures derived from PCM patients.

Material and methods. Genomic DNA from newly diagnosed 59 patients (without IgVH gene rearrangements and TP53 deletions) and 50 healthy blood donors were analyzed by RFLP-PCR to identify TP53 polymorphism. Chromosomal aberrations were detected by use of cIg-FISH. The lymphocyte cell cultures from a subgroup of 40 PCM patients were treated with bortezomib (1, 2 and 4 nM).

Results. The P allele of the P72R polymorphism was more common than the R allele in PMC patients compared to controls (39% vs. 24%), and the difference was significant (p = 0.02). The PP and PR genotypes (in combina­tion) were more frequent among cases than in controls (65% vs. 42%, OR = 2.32, p = 0.04). At the cell culture level and 2 nM bortezomib concentration the PP genotype was associated with higher necrosis rates (10.5%) compared to the PR genotype (5.7%, p = 0.006) or the RR genotype (6.3%, p = 0.02); however, no effect of genotypes was observed at bortezomib concentrations of 1 and 4 nM. The shortest OS (12 months) was observed in patients with the PP genotype compared to patients with the PR or RR genotypes (20 months) (p = 0.04).

Conclusions. The results suggest that P72R polymorphisms may be associated with an increased PCM risk and may affect OS of PCM patients. However, we saw no consistent results of the polymorphism effect on apoptosis and necrosis in cell cultures derived from PCM patients. Further studies are need in this regard.

Abstract

Introduction. Significant and accessible predictive factors for bortezomib treatment in plasma cell myeloma (PCM) are still lacking. TP53 codon 72 polymorphism (P72R) results in proline (P) or arginine (R) at 72 amino acid position, which causes synthesis of proteins with distinct functions. The aims of our study were to: 1) analyze whether this polymorphism is associated with an increased risk of PCM; 2) study whether the P72R polymorphism affects overall survival (OS) among PCM patients; 3) assess the possible association of the P72R polymorphism with sensitivity to bortezomib in cell cultures derived from PCM patients.

Material and methods. Genomic DNA from newly diagnosed 59 patients (without IgVH gene rearrangements and TP53 deletions) and 50 healthy blood donors were analyzed by RFLP-PCR to identify TP53 polymorphism. Chromosomal aberrations were detected by use of cIg-FISH. The lymphocyte cell cultures from a subgroup of 40 PCM patients were treated with bortezomib (1, 2 and 4 nM).

Results. The P allele of the P72R polymorphism was more common than the R allele in PMC patients compared to controls (39% vs. 24%), and the difference was significant (p = 0.02). The PP and PR genotypes (in combina­tion) were more frequent among cases than in controls (65% vs. 42%, OR = 2.32, p = 0.04). At the cell culture level and 2 nM bortezomib concentration the PP genotype was associated with higher necrosis rates (10.5%) compared to the PR genotype (5.7%, p = 0.006) or the RR genotype (6.3%, p = 0.02); however, no effect of genotypes was observed at bortezomib concentrations of 1 and 4 nM. The shortest OS (12 months) was observed in patients with the PP genotype compared to patients with the PR or RR genotypes (20 months) (p = 0.04).

Conclusions. The results suggest that P72R polymorphisms may be associated with an increased PCM risk and may affect OS of PCM patients. However, we saw no consistent results of the polymorphism effect on apoptosis and necrosis in cell cultures derived from PCM patients. Further studies are need in this regard.

Get Citation

Keywords

TP53 gene; polymorphism; plasma cell myeloma; bortezomib; apoptosis; necrosis

About this article
Title

TP53 polymorphism in plasma cell myeloma

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 55, No 4 (2017)

Article type

Original paper

Pages

203-211

Published online

2018-01-04

DOI

10.5603/FHC.a2017.0022

Pubmed

29333597

Bibliographic record

Folia Histochem Cytobiol 2017;55(4):203-211.

Keywords

TP53 gene
polymorphism
plasma cell myeloma
bortezomib
apoptosis
necrosis

Authors

Szymon Andrzej Zmorzynski
Iwona Korszen-Pilecka
Magdalena Wojcierowska-Litwin
Barbara Kwiatkowska-Drabik
Malgorzata Luterek
Sylwia Chocholska
Dorota Koczkodaj
Sylwia Popek
Malgorzata Michalak-Wojnowska
Grazyna Swiderska-Kolacz
Joanna Januszewska
Iwona Surowiec
Waldemar Tomczak
Marek Hus
Anna Dmoszynska
Marcin Pasiarski
Katarzyna Poniewierska-Jasak
Katarzyna Cieplinska
Olga Jankowska-Lecka
Agata Anna Filip

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