CEBPA mutations in acute myeloid leukemia: implications in risk stratification and treatment

• Published in: International journal of hematology 2024-11, Vol.120 (5), p.541-547
• Main Authors: Tien, Feng-Ming, Hou, Hsin-An
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; CCAAT-Enhancer-Binding Protein-alpha - genetics; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT/enhancer-binding protein; Classification; Cooperation; Cytogenetics; Drug development; Genes; Hematology; Humans; Internal medicine; Leucine; Leucine zipper proteins; Leukemia; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - therapy; Medical prognosis; Medicine; Medicine & Public Health; Mutation; Oncology; Patients; Precision medicine; Prognosis; Progress in Hematology; Proteins; Risk Assessment; Transcription factors
• ISSN: 0925-5710; 1865-3774; 1865-3774
• DOI: 10.1007/s12185-024-03773-5

Mutations in CCAAT enhancer binding protein α (CEBPA) occur in approximately 10% of patients with de novo acute myeloid leukemia (AML). Emerging evidence supports that in-frame mutations in the basic leucine zipper domain of CEBPA ( CEBPA bZIP−inf ) confer a survival benefit, and CEBPA bZIP−inf replaced CEBPA double mutations ( CEBPA dm ) as a unique entity in the 2022 World Health Organization (WHO-2022) classification and International Consensus Classification (ICC). However, challenges remain in daily clinical practice since more than 30% patients with CEBPA bZIP−inf die of AML despite intensive treatment. This review aims to provide a comprehensive summary of the heterogeneities observed in AML with CEBPA dm and CEBPA bZIP−inf , and will discuss the prognostic implications of concurrent mutations and novel mechanistic targets that may inform future drug development. The ultimate goal is to optimize clinical management and to provide precision medicine for this category of patients.