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

被引:54
作者
Anensen, N. [9 ]
Hjelle, S. M. [9 ]
Van Belle, W. [2 ]
Haaland, I. [9 ]
Silden, E. [9 ]
Bourdon, J-C [3 ]
Hovland, R. [4 ]
Tasken, K. [5 ,6 ]
Knappskog, S. [7 ,8 ]
Lonning, P. E. [7 ,8 ]
Bruserud, O. [9 ]
Gjertsen, B. T. [1 ,9 ]
机构
[1] Univ Bergen, Haukeland Univ Hosp, Hematol Sect, Dept Internal Med,Inst Med, N-5021 Bergen, Norway
[2] Norut IT, Tromso, Norway
[3] Univ Dundee, Sch Med, Dept Surg & Mol Oncol, Inserm European Associated Lab Inserm, Dundee, Scotland
[4] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway
[5] Univ Oslo, Biotechnol Ctr, Oslo, Norway
[6] Univ Oslo, Ctr Mol Med Norway, Nord EMBL Partnership, Oslo, Norway
[7] Univ Bergen, Sect Oncol, Inst Med, N-5021 Bergen, Norway
[8] Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway
[9] Univ Bergen, Inst Med, Hematol Sect, N-5021 Bergen, Norway
关键词
p53 protein isoform; p53; beta; gamma; acute myeloid leukemia/NPM1/FLT3-ITD; ACUTE MYELOGENOUS LEUKEMIA; AML; 10; FUNCTIONAL-CHARACTERIZATION; KINASE-ACTIVITY; CHEMOTHERAPY; GENE; NUCLEOPHOSMIN; ACTIVATION; PROGNOSIS; TRANSPLANTATION;
D O I
10.1038/onc.2011.348
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta and gamma expression. In conclusion, p53 biosignatures contain useful information for cancer evaluation and prognostication. Oncogene (2012) 31, 1533-1545; doi:10.1038/onc.2011.348; published online 22 August 2011
引用
收藏
页码:1533 / 1545
页数:13
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