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
- Authors
- Park, Sang Hyuk; Lee, Hyun Ji; Kim, In-Suk; Kang, Jeong-Eun; Lee, Eun Yup; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Won, Jong-Ho; Bang, Soo Mee; Kim, Hawk; Song, Moo-Kon; Chung, Joo Seop; Shin, Ho-Jin
- Issue Date
- May-2015
- Publisher
- 대한진단검사의학회
- Keywords
- Acute myeloid leukemia; Core binding factor; c-KIT; Epigenetic modification; Incidence; Prognosis; WT1
- Citation
- Annals of Laboratory Medicine, v.35, no.3, pp 288 - 297
- Pages
- 10
- Journal Title
- Annals of Laboratory Medicine
- Volume
- 35
- Number
- 3
- Start Page
- 288
- End Page
- 297
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/10716
- DOI
- 10.3343/alm.2015.35.3.288
- ISSN
- 2234-3806
2234-3814
- 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 (<= 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.
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