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

来源：

ONCOGENE | 2012年 / 31卷 / 12期

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

页码：1533 / 1545

页数：13

共 51 条

[1] Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients [J].

Aas, T ;

Borresen, AL ;

Geisler, S ;

SmithSorensen, B ;

Johnsen, H ;

Varhaug, JE ;

Akslen, LA ;

Lonning, PE .

NATURE MEDICINE, 1996, 2 (07) :811-814

[2] A distinct p53 protein isoform signature reflects the onset of induction chemotherapy for acute myeloid leukemia [J].

Anensen, Nina ;

Oyan, Anne Margrete ;

Bourdon, Jean-Christophe ;

Kalland, Karl Henning ;

Bruserud, Oystein ;

Gjertsen, Bjorn Tore .

CLINICAL CANCER RESEARCH, 2006, 12 (13) :3985-3992

[3] p53 isoforms can regulate p53 transcriptional activity [J].

Bourdon, JC ;

Fernandes, K ;

Murray-Zmijewski, F ;

Liu, G ;

Diot, A ;

Xirodimas, DP ;

Saville, MK ;

Lane, DP .

GENES & DEVELOPMENT, 2005, 19 (18) :2122-2137

[4] p53 mutant breast cancer patients expressing p53γ have as good a prognosis as wild-type p53 breast cancer patients [J].

Bourdon, Jean-Christophe ;

Khoury, Marie P. ;

Diot, Alexandra ;

Baker, Lee ;

Fernandes, Kenneth ;

Aoubala, Mustapha ;

Quinlan, Philip ;

Purdie, Colin A. ;

Jordan, Lee B. ;

Prats, Anne-Catherine ;

Lane, David P. ;

Thompson, Alastair M. .

BREAST CANCER RESEARCH, 2011, 13 (01)

[5]

Bruserud O, 2003, HAEMATOLOGICA, V88, P416

[6] p53 isoform Δ113p53 is a p53 target gene that antagonizes p53 apoptotic activity via BclxL activation in zebrafish [J].

Chen, Jun ;

Ng, Sok Meng ;

Chang, Changqing ;

Zhang, Zhenhai ;

Bourdon, Jean-Christophe ;

Lane, David P. ;

Peng, Jinrong .

GENES & DEVELOPMENT, 2009, 23 (03) :278-290

[7] CHEK2 Mutations Affecting Kinase Activity Together With Mutations in TP53 Indicate a Functional Pathway Associated with Resistance to Epirubicin in Primary Breast Cancer [J].

Chrisanthar, Ranjan ;

Knappskog, Stian ;

Lokkevik, Erik ;

Anker, Gun ;

Ostenstad, Bjorn ;

Lundgren, Steinar ;

Berge, Elisabet O. ;

Risberg, Terje ;

Mjaaland, Ingvil ;

Maehle, Lovise ;

Engebretsen, Lars Fredrik ;

Lillehaug, Johan Richard ;

Lonning, Per Eystein .

PLOS ONE, 2008, 3 (08)

[8] Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics:: interaction with other gene mutations [J].

Döhner, K ;

Schlenk, RF ;

Habdank, M ;

Scholl, C ;

Rücker, FG ;

Corbacioglu, A ;

Bullinger, L ;

Fröhling, S ;

Döhner, H .

BLOOD, 2005, 106 (12) :3740-3746

[9] Acute myeloid leukaemia [J].

Estey, Elihu ;

Doehner, Hartmut .

LANCET, 2006, 368 (9550) :1894-1907

[10] Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. [J].

Falini, B ;

Mecucci, C ;

Tiacci, E ;

Alcalay, M ;

Rosati, R ;

Pasqualucci, L ;

La Starza, R ;

Diverio, D ;

Colombo, E ;

Santucci, A ;

Bigerna, B ;

Pacini, R ;

Pucciarini, A ;

Liso, A ;

Vignetti, M ;

Fazi, P ;

Meani, N ;

Pettirossi, V ;

Saglio, G ;

Mandelli, F ;

Lo-Coco, F ;

Pelicci, P ;

Martelli, MF .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (03) :254-266

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