C/EBPA gene mutation and C/EBPA promoter hypermethylation in acute myeloid leukemia with normal cytogenetics.
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 wild-type 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- /NPM1- and is not associated with C/EBPA mutation.
Department of Pathology, City of Hope National Medical Center, Duarte, California 91010, USA.
Ying
Y
Lu
Wengang
W
Chen
Wei
W
Chen
Anthony
A
Stein
Lawrence M
LM
Weiss
Qin
Q
Huang
D000208:Acute Disease; D000328:Adult; D000368:Aged; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012306:Risk; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3