Double CEBPA mutations are prognostically favorable in non-M3 acute myeloid leukemia patients with wild-type NPM1 and FLT3-ITD.
This study is aimed to investigate the pattern of CEBPA mutations and its clinical significance in Chinese non-M3 acute myeloid leukemia (AML) patients. The entire coding region of CEBPA gene was amplified by PCR and then sequenced in samples from 233 non-M3 AML patients. Fifty mutations were identified in 37 (15.8%) patients with eleven (4.7%) double mutated CEBPA (dmCEBPA) and twenty-six (11.1%) single mutated CEBPA (smCEBPA). dmCEBPA was exclusively observed in M1 and M2 subtypes of FAB classification (P = 0.008), whereas smCEBPA occurred in almost all subtypes (P = 0.401). Patients with dmCEBPA had significantly younger age and higher WBC counts than those with wtCEBPA (P = 0.016 and 0.043, respectively). Both dmCEBPA and smCEBPA were mainly present in cytogenetically normal patients. Patients with dmCEBPA achieved higher rate of complete (CR) than wtCEBPA patients (88% vs. 51%, P = 0.037), whereas smCEBPA and wtCEBPA groups are similar (47% vs. 51%, P = 0.810). Patients with dmCEBPA had a superior overall survival (OS) compared with patients with wtCEBPA (P = 0.033), whereas patients with smCEBPA had a similar OS as patients with wtCEBPA (P = 0.976). dmCEBPA but not smCEBPA was also associated with favorable outcome in patients with wild-type NPM1 and FLT3-ITD (NPM1(wt)FLT3-ITD(wt) ). Our data confirm that dmCEBPA but not smCEBPA is prognostically favorable in NPM1(wt)FLT3-ITD(wt) AML, and suggest that the entity AML with mutated CEBPA should be definitely designated as AML with dmCEBPA in WHO classification and smCEBPA should be excluded from the favorable risk of molecular abnormalities.
Department of Hematology, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Xiang-Mei
XM
Wen
Laboratory Center, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Jiang
J
Lin
Department of Hematology, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Jing
J
Yang
Laboratory Center, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Dong-Ming
DM
Yao
Laboratory Center, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Zhao-Qun
ZQ
Deng
Department of Hematology, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Chun-Yan
CY
Tang
Laboratory Center, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Gao-Fei
GF
Xiao
Department of Hematology, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Lei
L
Yang
Laboratory Center, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Ji-Chun
JC
Ma
School of Medical Science and Laboratory Medicine, Jiangsu University Jiangsu 212013, Zhenjiang, People's Republic of China.
Jia-Bo
JB
Hu
Laboratory Center, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Wei
W
Qian
Department of Hematology, Affiliated People's Hospital of Jiangsu University Jiangsu 212002, Zhenjiang, People's Republic of China.
Jun
J
Qian
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D013997:Time Factors; 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
CEBPA; acute myeloid leukemia; mutation; prognosis