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MDM2 SNP309 promoter polymorphism, an independent prognostic factor in chronic lymphocytic leukemia

Willander, Kerstin; Ungerback, Jonas; Karlsson, Karin LU ; Fredrikson, Mats; Soderkvist, Peter and Linderholm, Mats (2010) In European Journal of Haematology1987-01-01+01:00 85(3). p.251-256
Abstract
Background: The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors. Objective: In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL). Patients: A total of 210 patients with B-CLL were followed for up to 19 yr. Results: The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar... (More)
Background: The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors. Objective: In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL). Patients: A total of 210 patients with B-CLL were followed for up to 19 yr. Results: The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar irrespective of MDM2 status. The presence of a G-allele in combination with TP53 mutations or unmutated IgVH gene status resulted in an additive risk of death. Conclusion: In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with OS. The survival difference was more pronounced in younger patients. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
prognostic, TP53 mutations, chronic lymphocytic leukemia, MDM2 SNP309, markers
in
European Journal of Haematology1987-01-01+01:00
volume
85
issue
3
pages
251 - 256
publisher
Wiley-Blackwell
external identifiers
  • wos:000280996400010
  • scopus:77955824152
ISSN
1600-0609
DOI
10.1111/j.1600-0609.2010.01470.x
language
English
LU publication?
yes
id
fff21998-116b-40f3-a23f-ef1aa14e4be4 (old id 1673848)
date added to LUP
2010-09-22 15:53:59
date last changed
2018-05-29 12:14:57
@article{fff21998-116b-40f3-a23f-ef1aa14e4be4,
  abstract     = {Background: The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors. Objective: In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL). Patients: A total of 210 patients with B-CLL were followed for up to 19 yr. Results: The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar irrespective of MDM2 status. The presence of a G-allele in combination with TP53 mutations or unmutated IgVH gene status resulted in an additive risk of death. Conclusion: In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with OS. The survival difference was more pronounced in younger patients.},
  author       = {Willander, Kerstin and Ungerback, Jonas and Karlsson, Karin and Fredrikson, Mats and Soderkvist, Peter and Linderholm, Mats},
  issn         = {1600-0609},
  keyword      = {prognostic,TP53 mutations,chronic lymphocytic leukemia,MDM2 SNP309,markers},
  language     = {eng},
  number       = {3},
  pages        = {251--256},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Haematology1987-01-01+01:00},
  title        = {MDM2 SNP309 promoter polymorphism, an independent prognostic factor in chronic lymphocytic leukemia},
  url          = {http://dx.doi.org/10.1111/j.1600-0609.2010.01470.x},
  volume       = {85},
  year         = {2010},
}