Aging and comprehensive molecular profiling in acute myeloid leukemia
Jianfeng Li, Wenyan Cheng, Xiangjie Lin, Xiangjie Lin, Lijun Wen, Kai Wang, Yongmei Zhu, Hongming Zhu, Xinjie Chen, Yuliang Zhang, Wei Yin, Jianan Zhang, Yi Xiao, Fan Zhang, Xiangqin Weng, Shengyue Wang, Lu Jiang, Hui-Yi Wu, Jiaqi Ren, Xiaojing Lin, Xiaojing Lin, Niu Qiao, Yuting Dai, Hai Fang, Yun Tan, Xiao‐Jian Sun, Gang Lv, Xiaoyu Yan, Suning Chen, Suning Chen, Zhu Chen, Jie Jin, Depei Wu, Ruibao Ren, Sai‐Juan Chen, Sai‐Juan Chen, Yang Shen
Abstract
Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion–negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA / B , platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.