Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemiaopen accessClinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia
- Other Titles
- Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia
- Authors
- 안서연; 김태형; 김미희; 송가영; 정성훈; 양덕환; 이제중; 김미연; 정철원; 장준호; 김희제; 문준호; 손상균; 원종호; 김성현; 김형준; 안재숙; 김동환
- Issue Date
- Jul-2023
- Publisher
- 대한암학회
- Keywords
- Leukemia; Myeloid; Acute; CEBPA; Next-generation sequencing; Allogeneic transplantation
- Citation
- Cancer Research and Treatment, v.55, no.3, pp 1011 - 1022
- Pages
- 12
- Journal Title
- Cancer Research and Treatment
- Volume
- 55
- Number
- 3
- Start Page
- 1011
- End Page
- 1022
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/25707
- DOI
- 10.4143/crt.2022.1407
- ISSN
- 1598-2998
2005-9256
- Abstract
- Purpose We evaluated the characteristics of CCAAT/enhancer-binding protein α (<i>CEBPA</i>) mutations and the significance of a basic leucine zipper in-frame mutation (bZIP<sup>in-f</sup>) of <i>CEBPA</i> in patients with acute myeloid leukemia with a normal karyotype.Materials and Methods Based on updated knowledge of <i>CEBPA</i> 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 bZIP<sup>in-f</sup> <i>CEBPA</i>, and 28 had non-bZIP<sup>in-f</sup> <i>CEBPA</i>. In the multivariate analysis, patients with <i>NPM1</i><sup>mut</sup>, those with bZIP<sup>in-f</sup> <i>CEBPA</i>, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but <i>FLT3</i>-ITD<sup>mut</sup> was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIP<sup>in-f</sup> <i>CEBPA</i>, and allo-HCT were associated with favorable outcomes; <i>FLT3</i>-ITD<sup>pos</sup> was associated with worse outcomes. In the <i>CEBPA</i> double-mutated group (<i>CEBPA</i><sup>dm</sup>), bZIP<sup>in-f</sup> <i>CEBPA</i> was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIP<sup>in-f</sup> <i>CEBPA</i>. Of 50 patients with bZIP<sup>in-f</sup> <i>CEBPA</i>, 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 bZIP<sup>in-f</sup> <i>CEBPA</i> 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 bZIP<sup>in-f</sup> <i>CEBPA</i> was associated with favorable outcomes in patients with <i>CEBPA</i><sup>dm</sup>. However, some mutations accompanying bZIP<sup>in-f</sup> <i>CEBPA</i> showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIP<sup>in-f</sup> <i>CEBPA<i>.
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