Proteomic subtypes enrich current acute myeloid leukemia nomenclature and reflect intrinsic pathogenesis alongside aging

作者：Wenyan Cheng, Xiao Yi, Zhenyi Wang, Jianfeng Li, Junyi Zhang, Ruihong Zhang, Qianqian Zhang, Xiangqin Weng, Ting Huang, Yongmei Zhu, Chao Wang, Wei Yin, Jianan Zhang, Hui-Yi Wu, Junmin Li, Hongming Zhu, Li Chen, Wenfang Wang, Yu-Ting Dai, Chenxu Gao, Xuan Liu, Shan Wang, Shengyue Wang, Bo Jiao, Zhu Chen, Hai Fang, Yin Tong, Yang Shen, Sai-Juan Chen · 发表于：Blood · 年份：2025 · DOI：10.1182/blood.2024027692 · 被引用次数：5 · 研究领域：Acute Myeloid Leukemia Research、Multiple Myeloma Research and Treatments、Myeloproliferative Neoplasms: Diagnosis and Treatment

ABSTRACT: Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy that increasingly affects the older population, with its posttranscriptional landscape remaining largely elusive. Establishing a stable proteomics-based classification system and systematically screening age-related proteins and regulatory networks are crucial for understanding the pathogenesis and outcomes of AML. In this study, we leveraged a multiomics cohort of 374 patients newly diagnosed with AML, integrating proteome, phosphoproteome, genome, transcriptome, and drug screening data. Through similarity network fusion clustering, we established 8 proteomic subtypes with distinct clinical and molecular properties, including S1 (CEBPA mutations), S3 (myelodysplasia-related AML), S4 (PML::RARA), S5 (NPM1 mutations), S6 (PML::RARA and RUNX1::RUNX1T1), S8 (CBFB::MYH11), S2 and S7 (mixed), aligning well with and adding actionable value to the latest World Health Organization nomenclature of AML. Hematopoietic lineage profiling of proteins indicated that megakaryocyte/platelet- and immune-related networks characterized distinct aging patterns in AML, which were consistent with our recent findings at the RNA level. Phosphosites also demonstrated distinct age-related features. The high protein abundance of megakaryocytic signatures was observed in S2, S3, and S7 subtypes, which were associated with advanced age and dismal prognosis of patients. A hematopoietic aging score with an independent ...