CEBPA polymorphisms and mutations in patients with acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and non-Hodgkin's lymphoma

被引：38

作者：

Fuchs, Ota ^{[1
]}

Provamikova, Dana ^{[1
]}

Kocova, Marcela ^{[1
]}

Kostecka, Arnost ^{[1
]}

Cvekova, Pavla ^{[1
]}

Neuwirtova, Radana ^{[2
]}

Kobylka, Petr ^{[1
]}

Cermak, Jaroslav ^{[1
]}

Brozinova, Jana ^{[1
]}

Schwarz, Jiri ^{[1
]}

Markova, Jana ^{[1
]}

Salaj, Peter ^{[1
]}

Klamova, Hana ^{[1
]}

Maaloufova, Jacqueline ^{[1
]}

Lemez, Petr ^{[3
]}

Novakova, Ludmila ^{[3
]}

Benesova, Katerina ^{[1
]}

机构：

[1] Inst Hematol & Blood Transfus, Dept Cell Physiol, CR-12820 Prague, Czech Republic

[2] Gen Fac Hosp, Prague, Czech Republic

[3] Fac Hosp Kralovske Vinohrady, Prague, Czech Republic

来源：

BLOOD CELLS MOLECULES AND DISEASES | 2008年 / 40卷 / 03期

关键词：

CEBPA mutations; acute myeloid leukemia; myelodysplastic syndrome; multiple myeloma; non-Hodgkin's lymphoma;

D O I：

10.1016/j.bcmd.2007.11.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The transcription factor CCAAT/enhancer binding protein (C/EBP)alpha is a myeloid-specific transcription factor which is required for normal myeloid differentiation. C/EBP alpha is encoded by an intronless gene that is 2783 bp long and maps to human chromosome 19q13.1. C/EBP alpha is a member of the basic region leucine zipper (bZIP) class of DNA-binding proteins. The loss of function of C/EBP alpha has leukemogenic potential. Four types of polymorphisms and 25 mutations (3 already known mutations and 22 novel mutations) were detected in CEBPA (gene for the transcription factor CCAAT/enhancer binding protein (C/EBP) a) in analysed samples from 390 patients with myelodysplastic syndrome (MDS) and hematologic malignancies. CEBPA mutations were found in 14/152 (9.2%) of acute myeloid leukemia (AML) patients' samples, 6/143 (4.2%) of MDS patients' samples, 2/56 (3.6%) of non-Hodgkin's lymphoma (NHL) patients' samples and 2/39 (5.1%) of multiple myeloma (MM) patients' samples. No C/ EBP alpha mutations were detected in healthy donors (41 individuals). We discuss how these mutations can affect the cellular function of C/EBPa and block the myeloid differentiation. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：401 / 405

页数：5

共 22 条

[1] The amino terminal and E2F interaction domains are critical for C/EBPα-mediated induction of granulopoietic development of hematopoietic cells [J].

D'Alo, F ;

Johansen, LM ;

Nelson, EA ;

Radomska, HS ;

Evans, EK ;

Zhang, P ;

Nerlov, C ;

Tenen, DG .

BLOOD, 2003, 102 (09) :3163-3171

[2] Increased hepatic cell proliferation and lung abnormalities in mice deficient in CCAAT/enhancer binding protein alpha [J].

Flodby, P ;

Barlow, C ;

Kylefjord, H ;

Åhrlund-Richter, L ;

Xanthopoulos, KG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (40) :24753-24760

[3] C/EBPα induces PU.1 and interacts with AP-1 and NF-κB to regulate myeloid development [J].

Friedman, Alan D. .

BLOOD CELLS MOLECULES AND DISEASES, 2007, 39 (03) :340-343

[4] CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics:: Prognostic relevance and analysis of cooperating mutations [J].

Fröhling, S ;

Schlenk, RE ;

Stolze, I ;

Bihlmayr, J ;

Benner, A ;

Kreitmeier, S ;

Tobis, K ;

Döhner, H ;

Döhner, K .

JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (04) :624-633

[5]

Fuchs O, 2007, FOLIA BIOL-PRAGUE, V53, P97

[6] Mutations in the gene encoding the transcription factor CCAAT/enhancer binding protein α in myelodysplastic syndromes and acute myeloid leukemias [J].

Gombart, AF ;

Hofmann, WK ;

Kawano, S ;

Takeuchi, S ;

Krug, U ;

Kwok, SH ;

Larsen, RJ ;

Asou, H ;

Miller, CW ;

Hoelzer, D ;

Koeffler, HP .

BLOOD, 2002, 99 (04) :1332-1340

[7] Transcription activation function of C/EBPα is required for induction of granulocytic differentiation [J].

Keeshan, K ;

Santilli, G ;

Corradini, F ;

Perrotti, D ;

Calabretta, B .

BLOOD, 2003, 102 (04) :1267-1275

[8] CEBPα mutations in childhood acute myeloid leukemia [J].

Liang, DC ;

Shih, LY ;

Huang, CF ;

Hung, IJ ;

Yang, CP ;

Liu, HC ;

Jaing, TH ;

Wang, LY ;

Chang, WH .

LEUKEMIA, 2005, 19 (03) :410-414

[9] Characterization of CEBPA mutations in acute myeloid leukemia:: Most patients with CEBPA mutations have biallelic mutations and show a distinct immunophenotype of the leukemic cells [J].

Lin, LI ;

Chen, CY ;

Lin, DT ;

Tsay, W ;

Tang, JL ;

Yeh, YC ;

Shen, HL ;

Su, FH ;

Yao, M ;

Huang, SY ;

Tien, HF .

CLINICAL CANCER RESEARCH, 2005, 11 (04) :1372-1379

[10] Transcriptional dysregulation during myeloid transformation in AML [J].

Pabst, T. ;

Mueller, B. U. .

ONCOGENE, 2007, 26 (47) :6829-6837

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