Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy response in acute myeloid leukemia

Nina Ånensen¹ - nina.anensen@med.uib.no
Werner Van Belle² - werner@yellowcouch.org, werner.van.belle@gmail.com
S.M. Hjelle¹
Ingvild Haaland¹ - ingvild.haaland@student.uib.no
E Silden
Jean-Christophe Bourdon
R Hovland¹
K Taskén
S Knappskog
P.E. Lønning
Oystein Bruserud
Bjørn Tore Gjertsen¹ - bjorn.gjertsen@med.uib.no

1- Institute of Medicine Hematology Section University of Bergen Haukeland University Hospital; Bergen; Norway
2- Internet & Communication Technology Norut IT; Research Park; 9294 Tromsø; Norway

* Corresponding author

Abstract :  The wild-type tumor-suppressor gene TP53 encodes several isoforms of the p53 protein. However, while the role of p53 in controlling normal cell cycle progression and tumor suppression is well established, the clinical significance of p53 isoform expression is unknown. A novel bioinformatic analysis of p53 isoform expression in 68 patients with acute myeloid leukemia revealed distinct p53 protein biosignatures correlating with clinical outcome. Furthermore, we show that mutated FLT3, a prognostic marker for short survival in AML, is associated with expression of full-length p53. In contrast, mutated NPM1, a prognostic marker for long-term survival, correlated with p53 isoforms ? and ? expression. In conclusion, p53 biosignatures contain useful information for cancer evaluation and prognostication.

Keywords:  p53 isoforms, leukemia, correlation analysis, 2D gels
Reference:  Nina Ånensen, Werner Van Belle, S.M. Hjelle, Ingvild Haaland, E Silden, Jean-Christophe Bourdon, R Hovland, K Taskén, S Knappskog, P.E. Lønning, Oystein Bruserud, Bjørn Tore Gjertsen; Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy response in acute myeloid leukemia; Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy response in acute myeloid leukemia; Nature Oncogene; volume 31; pages 1533-1545; March 2012