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Implications of the 5th Edition of the World Health Organization Classification and International Consensus Classification of Myeloid Neoplasm in Myelodysplastic Syndrome With Excess Blasts and Acute Myeloid Leukemia
2023; 43(5): 503-507
Article
Original Article
Ann Lab Med 2015; 35(3): 288-297
Published online May 1, 2015 https://doi.org/10.3343/alm.2015.35.3.288
Copyright © Korean Society for Laboratory Medicine.
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
Sang Hyuk Park, M.D.1,*, Hyun Ji Lee, M.D.2,*, In-Suk Kim, M.D.3, Jeong-Eun Kang, M.D.4, Eun Yup Lee, M.D.1, Hyeoung-Joon Kim, M.D.5, Yeo-Kyeoung Kim, M.D.5, Jong-Ho Won, M.D.6, Soo Mee Bang, M.D.7, Hawk Kim, M.D.8, Moo-Kon Song, M.D.9, Joo Seop Chung, M.D.9, and Ho-Jin Shin, M.D.9
Department of Laboratory Medicine1, Pusan National University School of Medicine, Pusan National University Hospital, Biomedical Research Institute, Pusan National University Hospital, Busan; Department of Laboratory Medicine2, Korean Red cross, Changwon; Department of Laboratory Medicine3, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan; Department of Laboratory Medicine4, Jinhae Yonsei Hospital, Changwon; Department of Hematology-Oncology5, Chonnam National University Hwasun Hospital, Hwasun; Department of Hematology-Oncology6, Soonchunhyang University Hospital, Seoul; Department of Hematology-Oncology7, Seoul National University Bundang Hospital, Seongnam; Department of Hematology-Oncology8, Ulsan University Hospital, Ulsan; Division of Hematology-Oncology9, Department of Internal Medicine, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
Correspondence to: Ho-Jin Shin
Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Korea
Tel: +82-51-240-7839
Fax: +82-51-247-6560
E-mail: hojinja@hanmail.net
*These two authors contributed equally to this work as first authors.
Received: September 1, 2014; Revised: November 24, 2014; Accepted: February 13, 2015
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: Acute myeloid leukemia, Core binding factor, c-KIT, Epigenetic modification, Incidence, Prognosis, WT1