Incidences and Prognostic Impact of c-KIT, WT1, CEBPA, and CBL Mutations, and Mutations Associated With Epigenetic Modification in Core Binding Factor Acute Myeloid Leukemia: A Multicenter Study in a Korean Population.
10.3343/alm.2015.35.3.288
- Author:
Sang Hyuk PARK
1
;
Hyun Ji LEE
;
In Suk KIM
;
Jeong Eun KANG
;
Eun Yup LEE
;
Hyeoung Joon KIM
;
Yeo Kyeoung KIM
;
Jong Ho WON
;
Soo Mee BANG
;
Hawk KIM
;
Moo Kon SONG
;
Joo Seop CHUNG
;
Ho Jin SHIN
Author Information
1. Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Acute myeloid leukemia;
Core binding factor;
c-KIT;
Epigenetic modification;
Incidence;
Prognosis;
WT1
- MeSH:
Adolescent;
Adult;
Aged;
Aged, 80 and over;
Asian Continental Ancestry Group/*genetics;
CCAAT-Enhancer-Binding Proteins/*genetics;
Child;
Core Binding Factors/genetics;
Disease-Free Survival;
Epigenesis, Genetic;
Female;
Humans;
Incidence;
Leukemia, Myeloid, Acute/*diagnosis/epidemiology/genetics;
Male;
Middle Aged;
Mutation;
Prognosis;
Proto-Oncogene Proteins c-cbl/*genetics;
Proto-Oncogene Proteins c-kit/*genetics;
Republic of Korea/epidemiology;
Survival Rate;
Translocation, Genetic;
WT1 Proteins/*genetics;
Young Adult
- From:Annals of Laboratory Medicine
2015;35(3):288-297
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: To identify potential molecular prognostic markers in core binding factor (CBF) AML, we analyzed incidences and prognostic impacts of mutations in c-KIT, WT1, CEBPA, CBL, and a number of epigenetic genes in CBF AML. METHODS: Seventy one and 21 AML patients with t(8;21) and inv(16) were enrolled in this study, respectively. NPM1, CEBPA, c-KIT, IDH1/2, DNMT3A, EZH2, WT1, and CBL mutations were analyzed by direct sequencing. Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared. RESULTS: The incidences of FLT3 internal tandem duplication (ITD), NPM1, CEBPA, IDH1/2, DNMT3A, EZH2, and CBL mutations were low (< or =5%) in CBF AML patients. However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly. Relapse or death during follow-up occurred more frequently in t(8;21) patients carrying c-KIT mutations than in those without the mutation, although the difference was significant only in a specific patient subgroup with no WT1 mutations (P=0.014). CONCLUSIONS: The incidences of mutations in epigenetic genes are very low in CBF AML; however, c-KIT and WT1 mutations occur more frequently than others. The poor prognostic impact of c-KIT mutation in t(8;21) AML patients only applies in a specific patient subgroup without WT1 mutations. The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.
