https://scholars.lib.ntu.edu.tw/handle/123456789/639807
標題: | Dysregulated immune and metabolic pathways are associated with poor survival in adult acute myeloid leukemia with CEBPA bZIP in-frame mutations | 作者: | FENG-MING TIEN CHI-YUAN YAO Tsai, Xavier Cheng-Hong Lo, Min-Yen Chen, Chien-Yuan WAN-HSUAN LEE CHIEN-CHIN LIN Kuo, Yuan-Yeh Peng, Yen-Ling Tseng, Mei-Hsuan Wu, Yu-Sin Liu, Ming-Chih LIANG-IN LIN MING-KAI CHUANG BOR-SHENG KO MING YAO Tang, Jih-Luh WEN-CHIEN CHOU HSIN-AN HOU HWEI-FANG TIEN |
公開日期: | 23-一月-2024 | 卷: | 14 | 期: | 1 | 來源出版物: | Blood cancer journal | 摘要: | Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPAbZIP-inf) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPAbZIP-inf. One hundred and thirteen CEBPAbZIP-inf patients were identified in a cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Concurrent WT1 or DNMT3A mutations significantly predicted worse survival in AML patients with CEBPAbZIP-inf. RNA-sequencing analysis revealed an enrichment of interferon (IFN) signaling and metabolic pathways in those with a shorter event-free survival (EFS). CEBPAbZIP-inf patients with a shorter EFS had higher expression of IFN-stimulated genes (IRF2, IRF5, OAS2, and IFI35). Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPAbZIP-inf, and upfront allogeneic transplantation may be indicated for better long-term disease control. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/639807 | ISSN: | 2044-5385 | DOI: | 10.1038/s41408-023-00975-8 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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