Renmin Hospital of Wuhan University, Wuhan, China.
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie-fang Avenue, Wuhan, 430030, Hubei, China.
Clin Epigenetics. 2024 Jan 22;16(1):16. doi: 10.1186/s13148-024-01627-9.
Decitabine has been widely used to treat acute myeloid leukemia (AML); however as AML is a heterogeneous disease, not all patients benefit from decitabine. This study aimed to identify markers for predicting the response to decitabine.
An intersection of in vitro experiments and bioinformatics was performed using a combination of epigenetic and transcriptomic analysis. A tumor-suppressor gene associated with methylation and the response to decitabine was screened. Then the sensitivity and specificity of this marker in predicting the response to decitabine was confirmed in 54 samples from newly diagnosed AML patients treated with decitabine plus IA regimen in a clinical trial (ChiCTR2000037928).
In vitro experiments showed that decitabine caused hypomethylation and upregulation of BTG1, while downregulation of BTG1 attenuated the inhibitory effect of decitabine. In newly diagnosed AML patients who received decitabine plus IA regimen, the predictive value of BTG1 to predict complete remission (CR) was assigned with a sensitivity of 86.7% and a specificity of 100.0% when BTG1 expression was < 0.292 (determined using real-time quantitative PCR), with area under the curve (AUC) = 0.933, P = 0.021. The predictive value of BTG1 to predict measurable residual disease (MRD) negativity was assigned with a sensitivity of 100.0% and a specificity of 80.0% when BTG1 expression was < 0.292 (AUC = 0.892, P = 0.012). Patients were divided into low and high BTG1 expression groups according to a cutoff of 0.292, and the CR rate of the low-expression group was significantly higher than that of the high-expression group (97.5% vs. 50%, P < 0.001).
Low expression of BTG1 was associated with CR and MRD negativity in newly diagnosed AML patients treated with a decitabine-containing regimen, suggesting that BTG1 is a potential marker for predicting the response to decitabine in newly diagnosed AML.
ChiCTR2000037928.
地西他滨已被广泛用于治疗急性髓系白血病（AML）；然而，由于 AML 是一种异质性疾病，并非所有患者都能从地西他滨治疗中获益。本研究旨在确定预测地西他滨反应的标志物。
采用表观遗传学和转录组学分析相结合的方法进行体外实验和生物信息学的交叉研究。筛选出与甲基化和对地西他滨反应相关的肿瘤抑制基因。然后，在一项临床试验中，对 54 例新诊断的 AML 患者接受地西他滨联合 IA 方案治疗的样本进行了该标志物对地西他滨反应预测的敏感性和特异性验证（ChiCTR2000037928）。
体外实验表明，地西他滨引起 BTG1 的低甲基化和上调，而 BTG1 的下调减弱了地西他滨的抑制作用。在接受地西他滨联合 IA 方案治疗的新诊断 AML 患者中，当 BTG1 表达<0.292 时（采用实时定量 PCR 测定），BTG1 对预测完全缓解（CR）的预测值具有 86.7%的敏感性和 100.0%的特异性，曲线下面积（AUC）=0.933，P=0.021。当 BTG1 表达<0.292 时（AUC=0.892，P=0.012），BTG1 对预测可测量残留疾病（MRD）阴性的预测值具有 100.0%的敏感性和 80.0%的特异性。根据 0.292 的截断值，将患者分为低表达和高表达 BTG1 两组，低表达组的 CR 率明显高于高表达组（97.5%比 50%，P<0.001）。
在接受地西他滨治疗的新诊断 AML 患者中，BTG1 低表达与 CR 和 MRD 阴性相关，提示 BTG1 是预测新诊断 AML 对地西他滨反应的潜在标志物。
ChiCTR2000037928。
