In:
Cancer Research and Treatment, Korean Cancer Association, Vol. 55, No. 3 ( 2023-07-15), p. 1011-1022
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 〉 .
Type of Medium:
Online Resource
ISSN:
1598-2998
,
2005-9256
DOI:
10.4143/crt.2022.1407
Language:
English
Publisher:
Korean Cancer Association
Publication Date:
2023
detail.hit.zdb_id:
2514151-X
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