CEBPA bZIP in-frame mutations in acute myeloid leukemia: prognostic and therapeutic implications

作者：Fenghong Zhang, Zhen Shen, Jundan Xie, Jing-Ren Zhang, Qian Wu, Rui Jiang, Xiangyu Zhao, Xiaofei Yang, Suning Chen · 发表于：Blood Cancer Journal · 年份：2024 · DOI：10.1038/s41408-024-01042-6 · 被引用次数：8 · 研究领域：Acute Myeloid Leukemia Research、Acute Lymphoblastic Leukemia research、Retinoids in leukemia and cellular processes

The transcription factor CCAAT/enhancer-binding protein-alpha( CEBPA ) is a critical mediator of granulocytic differentiation. Mutations of the CEBPA gene ( CEBPA mut ) occur in 5%–15% of adult AML patients and in-frame mutations within the bZIP domain of CEBPA ( CEBPA bZIP-inf ) define a distinct entity associated with favorable prognosis in AML patients when treated by conventional chemotherapy [ 1 , 2 ]. CEBPA mutations could activate the BCL2 P2 promoter and induce its expression via interaction with nuclear factor-κB (NF-κB) p50 in hematopoietic cell lines and display a markedly hypermethylated profile by multi-omics analysis in primary leukemia cells [ 3 , 4 , 5 ]. Meanwhile, venetoclax plus hypomethylating agents (VEN + HMA) were efficient in AML patients with specific molecular profiles (such as NPM1 , IDH2 , etc.) [ 6 , 7 ]. However, relevant data related to the role of VEN + HMA regimens in CEBPA bZIP-inf AML patients is limited. Therefore, in the current study, we retrospectively analyzed the clinical features, co-mutational spectrum, and prognostic role of CEBPA mutations, particularly CEBPA bZIP-inf mutations, in 996 newly diagnosed adult AML patients inducted with chemo-free regimens or chemotherapy between 2016–2022 at the First Affiliated Hospital of Soochow University in China.