Department of Hematology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, 157 Xiwu Road, Xincheng District, Xi'an, Shaanxi 710004, PR China.
Department of Genetics and Molecular Biology, Medical school of Xi'an Jiaotong University/Key Laboratory of Environment and Disease-Related Gene, Ministry of Education, 76 Western Yanta Road, Xi'an, Shaanxi 710061, PR China.
Proteome Sci. 2013 Aug 3;11:39. doi: 10.1186/1477-5956-11-39. eCollection 2013.
Post treatment minimal residual disease (MRD) determination contributes to impending relapse prediction, chemotherapy response and clinical outcomes assessment, guiding clinicians to develop reasonable and effective individual chemotherapy options after induction/consolidation. This study was to identify serum candidate peptides for monitoring adult acute myeloid leukemia (AML) MRD.
47 statistically different expressed peptide peaks were obtained in the molecular weight range of 700-10000 Da. Quick classifier (QC) model had optimal distinction efficiency, in the training set with a sensitivity of 90% and a specificity of 93.33%. Peptides were identified as ubiquitin-like modifier activating enzyme 1(UBA1), isoform 1 of fibrinogen alpha chain precursor and platelet factor 4(PF4). The peptide up-regulated in newly diagnosed AML patients were decreased to the normal level after CR. When refractory & relapsed, relative intensity was elevated again. Results were contrary to down-regulated peptide peaks. Western blot demonstrated that levels of the UBA1 protein did not differ between the leukemia and normal cells. Levels of isoform 1 of fibrinogen alpha chain precursor protein and PF4 protein were both decreased in leukemia cells comparing with normal cells. The serum levels of the PF4 in the newly diagnosed AML patients and healthy controls were significantly different. Further correlation analysis did not indicate the correlated relation between platelet counts and PF4 content, the correlation coefficient was 0.097. Kaplan-Meier analyses of overall survival showed that relative intensity of peptides was correlated with patient's clinical outcome.
We speculate the peptides can be used as potential markers for monitoring minimal residual disease and clinical outcome assessment.
治疗后微小残留病（MRD）的测定有助于预测即将发生的复发，评估化疗反应和临床结果，指导临床医生在诱导/巩固后制定合理有效的个体化化疗方案。本研究旨在鉴定用于监测成人急性髓系白血病（AML）MRD 的血清候选肽。
在 700-10000 Da 的分子量范围内获得了 47 个具有统计学差异的表达肽峰。快速分类器（QC）模型具有最佳的区分效率，在训练集中，其敏感性为 90%，特异性为 93.33%。肽被鉴定为泛素样修饰酶激活酶 1（UBA1）、纤维蛋白原α链前体同工型 1 和血小板因子 4（PF4）。在新诊断的 AML 患者中上调的肽在 CR 后降低到正常水平。当耐药和复发时，相对强度再次升高。结果与下调的肽峰相反。Western blot 表明白血病和正常细胞之间 UBA1 蛋白水平没有差异。纤维蛋白原α链前体蛋白同工型 1 和 PF4 蛋白的水平在白血病细胞中均低于正常细胞。新诊断的 AML 患者和健康对照者的血清 PF4 水平差异显著。进一步的相关性分析表明血小板计数与 PF4 含量之间没有相关性，相关系数为 0.097。总体生存的 Kaplan-Meier 分析表明，肽的相对强度与患者的临床结果相关。
我们推测这些肽可用作监测微小残留病和临床结果评估的潜在标志物。
