K313dup is a recurrent CEBPA mutation in de novo acute myeloid leukemia (AML)

被引：0
作者：
Maria J. Carnicer
Adriana Lasa
Marcus Buschbeck
Elena Serrano
Maite Carricondo
Salut Brunet
Anna Aventin
Jorge Sierra
Luciano Di Croce
Josep F. Nomdedeu
机构：
[1] Universitat Autònoma de Barcelona,Department of Hematology, Hospital de la Santa Creu i Sant Pau
[2] Universitat Pompeu Fabra,Centre de Regulacio Genomica (CRG)
[3] ICREA and Centre de Regulacio Genomica (CRG),Laboratori d’Hematologia, Hospital de la Santa Creu i Sant Pau
[4] Universitat Autònoma de Barcelona,undefined
来源：
Annals of Hematology | 2008年 / 87卷
关键词：
CEBPA; Acute myeloid leukemia; Mutations;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The CEBPA gene codes for a transcription factor that has a pivotal role in controlling proliferation and differentiation of myeloid progenitors. Acquired CEBPA mutations have been found in acute myeloid leukemias (AML) with a good prognosis, and most of these patients have a normal karyotype. In this paper, we report four cases that displayed the same K313dup in the CEBPA gene. All four had an AML-M1 with CD7 positivity and T-cell receptor gamma chain (TCR-γ) rearrangement. This mutation could represent nearly 10% of all CEBPA mutations described to date. K313dup disappeared in samples from patients in complete remission. In transfected cells, the K313dup mutant had reduced protein stability with respect to the wild-type protein. K313dup seems to be selected in leukemic cells, and its frequency in other AML series could be determined using the screening method reported in this paper.
引用
收藏
页码：819 / 827
页数：8
相关论文
共 252 条
[1]  
Antonson P(1995)Molecular cloning, sequence, and expression patterns of the human gene encoding CCAAT/enhancer binding protein alpha (C/EBP alpha) Biochem Biophys Res Commun 215 106-113.
[2]  
Xanthopoulos KG(2001)Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia Nat Genet 27 263-270
[3]  
Pabst T(2002)Mutations in the gene encoding the transcription factor CCAAT/enhancer binding protein alpha in myelodysplastic syndromes and acute myeloid leukemias Blood 99 1332-1340
[4]  
Mueller BU(2005)Development of a human acute myeloid leukaemia screening panel and consequent identification of novel gene mutation in FLT3 and CCND3 Br J Haematol 128 318-323
[5]  
Zhang P(1998)CCAAT/enhancer binding protein alpha is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors Mol Cell Biol 18 4301-4314
[6]  
Radomska HS(2001)c-Myc is a critical target for c/EBPalpha in granulopoiesis Mol Cell Biol 21 3789-3806
[7]  
Narravula S(2001)AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia Nat Med 7 444-451
[8]  
Schnittger S(1998)The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation Mol Cell Biol 18 322-333
[9]  
Gombart AF(2003)Down-modulation of the C/EBPalpha transcription factor in core binding factor acute myeloid leukemias Blood 102 2705-2706
[10]  
Hofmann WK(2004)The leukemic fusion gene AML1-MDS1-EVI1 suppresses CEBPA in acute myeloid leukemia by activation of Calreticulin Proc Natl Acad Sci U S A 101 13312-13317
12345678910