Clinical Significance of bZIP in-Frame <i>CEBPA</i>-Mutated Normal Karyotype Acute Myeloid Leukemia

Ahn, Seo-Yeon; Kim, TaeHyung; Kim, Mihee; Song, Ga-Young; Jung, Sung-Hoon; Yang, Deok-Hwan; Lee, Je-Jung; Kim, Mi Yeon; Jung, Chul Won; Jang, Jun-Ho; Kim, Hee Je; Moon, Joon Ho; Sohn, Sang Kyun; Won, Jong-Ho; Kim, Sung-Hyun; Kim, Hyeoung-Joon; Ahn, Jae-Sook; Kim, Dennis Dong Hwan

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Cancer Research and Treatment > Accepted Articles

Original Article

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 Kim^2,3, 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 Kim^1,4, Jae-Sook Ahn^1,4

, 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.

ABSTRACT

Purpose
We evaluated the characteristics of CEBPA mutations and the significance of a basic leucine zipper in-frame mutation (bZIP^in-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.
Results
Among 78 of a total of 395 patients (19.7%), 50 had bZIP^in-f CEBPA, and 28 had non-bZIP^in-f CEBPA. In the multivariate analysis, patients with NPM1^mut, those with bZIP^in-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITD^mut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIP^in-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITD^pos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPA^dm), bZIP^in-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIP^in-f CEBPA. Of 50 patients with bZIP^in-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 bZIP^in-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).
Conclusion
Only bZIP^in-f CEBPA was associated with favorable outcomes in patients with CEBPA^dm. However, some mutations accompanying bZIP^in-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIP^in-f CEBPA.

Key words: Leukemia, Myeloid, Acute, CEBPA, NGS, Allogeneic Transplantation