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Original Article
- Hematologic malignancy
- Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia
- Seo-Yeon Ahn, TaeHyung Kim, Mihee Kim, Ga-Young Song, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Hyeoung-Joon Kim, Jae-Sook Ahn, Dennis Dong Hwan Kim
- Cancer Res Treat. 2023;55(3):1011-1022. Published online January 26, 2023
- DOI: https://doi.org/10.4143/crt.2022.1407
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Abstract
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ePub - Purpose
We evaluated the characteristics of CCAAT/enhancer-binding protein α (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 CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.
Results
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=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838).
Conclusion
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. -
Citations
Citations to this article as recorded by
- Prognostic value of CEBPA bZIP signatures in cytogenetically normal acute myeloid leukaemia
Li‐Xin Wu, Ming‐Yue Liao, Ming‐Yue Zhao, Nan Yan, Ping Zhang, Li‐Xia Liu, Jia‐Yue Qin, Shan‐Bo Cao, Jia Feng, Qian Jiang, Ying‐Jun Chang, Lan‐Ping Xu, Xiao‐Hui Zhang, Xiao‐Jun Huang, Hao Jiang, Hong‐Yu Zhang, Guo‐Rui Ruan
British Journal of Haematology.2025;[Epub] CrossRef -
CEBPA double mutations associated with ABO antigen weakness in hematologic diseases
Seung Jun Choi, Hyun Kyung Kim, Eun Jung Suh, Soon Sung Kwon, Saeam Shin, Seung-Tae Lee, Sinyoung Kim
Blood Advances.2024; 8(6): 1487. CrossRef - CEBPA bZIP in-frame mutations in acute myeloid leukemia: prognostic and therapeutic implications
Fenghong Zhang, Zhen Shen, Jundan Xie, Jingren Zhang, Qian Wu, Rui Jiang, Xiangyu Zhao, Xiaofei Yang, Suning Chen
Blood Cancer Journal.2024;[Epub] CrossRef - Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia
Juan Carlos Rivera, Daniel Nuñez, Elizabet Millar, Kimberly Ramirez, Mauricio Chandía, Claudio Aguayo
International Journal of Laboratory Hematology.2023; 45(6): 833. CrossRef
- Prognostic value of CEBPA bZIP signatures in cytogenetically normal acute myeloid leukaemia
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