C/EBPA gene mutation and C/EBPA promoter hypermethylation in acute myeloid leukemia with normal cytogenetics

被引:17
作者
Lu, Ying [1 ,2 ]
Chen, Wengang [1 ]
Chen, Wei [1 ,3 ]
Stein, Anthony
Weiss, Lawrence M. [1 ]
Huang, Qin [1 ]
机构
[1] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA
[2] Ningbo NO 1 Hosp, Dept Hematol, Ningbo, Zhejiang, Peoples R China
[3] Zhejiang Univ, Coll Med, Sir Run Run Hosp, Dept Oncol, Hangzhou 310003, Zhejiang, Peoples R China
关键词
BINDING-PROTEIN-ALPHA; CEBPA MUTATIONS; PROGNOSTIC-SIGNIFICANCE; TUMOR-SUPPRESSOR; YOUNGER ADULTS; DIFFERENTIATION; EXPRESSION; AML; LEUKEMOGENESIS; FEATURES;
D O I
10.1002/ajh.21706
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the current study, we investigated C/EBPA gene mutations and promoter hypermethylation in a series of 53 patients with CN-AML. In addition, we also analyzed two other frequent mutations (FLT3/ITD and NPM1) in these patients and correlated them with C/EBPA gene alterations. 13/53 patients were FLT3/ITD+/NPM1-, 11/53 patients were FLT3/ITD+/NPM1+, 9/53 patients were FLT3/ITD-/NPM1+, and 20/53 patients were FLT3/ITD-/NPM1-. Four of 53 cases displayed C/EBPA mutations, whereas 49 cases had only C/EBPA wildtype alleles. Of the four positive cases, three patients had N-terminal mutations only, whereas one patient had mutations in both the N- and C-terminal region. Two of the four positive cases also harbored both FLT3/ITD and NPM1 mutation simultaneously, whereas the other two patients had neither FLT3/ITD nor NPM1 mutations. Furthermore, 7/53 cases displayed C/EBPA promoter hypermethylation. Interestingly, they were all in CN-AML cases without FLT3/ITD or NPM1 mutations. None of the seven patients with C/EBPA promoter hypermethylation showed C/EBPA mutation. In conclusion, C/EBPA mutation and promoter hypermethylation can be detected at a relatively low frequency in de novo CN-AML patients, suggesting they may contribute to leukemogenesis. C/EBPA mutation appears to be seen in "high-risk" AML (FLT3/ITD+/NPM1+; FLT3/ITD+/NPM1- or FLT3/ITD-/NPM1-), while C/EBPA hypermethylation appears to be more common in AML with FLT3/ITD- INPM1- and is not associated with C/EBPA mutation. Am. J. Hematol. 85:426-430, 2010. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:426 / 430
页数:5
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