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Cancer Research and Treatment > Accepted Articles
doi: https://doi.org/10.4143/crt.2022.1407    [Accepted]
Clinical Significance of bZIP in-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia
Seo-Yeon Ahn1 , TaeHyung Kim2,3, Mihee Kim1, Ga-Young Song1, Sung-Hoon Jung1, Deok-Hwan Yang1, Je-Jung Lee1, Mi Yeon Kim4, Chul Won Jung5, Jun-Ho Jang5, Hee Je Kim6, Joon Ho Moon7, Sang Kyun Sohn7, Jong-Ho Won8, Sung-Hyun Kim9, Hyeoung-Joon Kim1,4, Jae-Sook Ahn1,4 , Dennis Dong Hwan Kim10
1Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea
2The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada
3Department of Computer Science, University of Toronto, Toronto, Canada
4Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Korea
5Division of Hematology-Oncology, Samsung Medical Center, Seoul, Korea
6Department of Hematology, Cancer Research Institute, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
7Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, Korea
8Department of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, Korea
9Department of Hematology-Oncology, Dong-A University College of Medicine, Busan, Korea
10Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada
Correspondence  Jae-Sook Ahn ,Tel: 82-61-379-7635, Fax: 82-61-379-7628, Email: f0115@jnu.ac.kr
Received: October 25, 2022;  Accepted: January 24, 2023.  Published online: January 26, 2023.
We evaluated the characteristics of CEBPA mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype.
Materials and Methods
Based on updated knowledge of CCAAT/enhancer-binding protein α (CEBPA) mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.
Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.020, hazard ratio (HR):2.775) and a trend in inferior RFS (p=0.106, HR:2.106).
Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.
Key words: Leukemia, Myeloid, Acute, CEBPA, NGS, Allogeneic Transplantation
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