Prognostic value of BTG1 for predicting decitabine sensitivity in de novo acute myeloid leukemia.
Shiyuan Zhang, Mengyuan Li, Bin Xu, Xiaojian Zhu, Xia Mao, Hao Zhou, Xiwen Tong, Shuai Su, Yi Zhu, Donghua Zhang
Abstract
Open AccessDecitabine has demonstrated efficacy in the treatment of acute myeloid leukemia (AML), though therapeutic responses vary widely due to the disease's inherent heterogeneity. To address this clinical challenge, we aimed to identify reliable biomarkers for predicting decitabine responsiveness in patients with AML. In our previous studies, integrated epigenetic and transcriptomic profiling identified BTG1 as a methylation-associated tumor suppressor gene correlated with decitabine sensitivity. We found that decitabine upregulates BTG1 expression through demethylation, and this upregulation enhances the sensitivity of AML cells to decitabine. BTG1 may exert its effect through the Wnt/β-catenin signaling pathway. Notably, BTG1 expression levels were significantly associated with treatment outcomes, including complete remission (CR) rates and measurable residual disease (MRD) negativity in patients receiving decitabine-containing regimens (either "7 + 3" or alternative combinations). Importantly, peripheral blood BTG1 mRNA expression levels reliably predicted therapeutic response to decitabine, establishing BTG1 as a robust biomarker of decitabine efficacy in AML management. Clinical trial registration: ChiCTR2000037928.