中文摘要：

目的根据急性白血病（AL）患者与健康人血清多肽图的差异，筛选用于AL微小残留病（MRD）监测的血清标志物。方法应用铜螯合磁珠法富集AL患者、健康人及良性血液病患者血清中的多肽，用基质辅助激光解吸电离飞行时间质谱仪（MALDI-TOFMS）检测获取血清多肽图，并分析差异多肽的表达。结果根据AL患者与健康人每个血清多肽经t检验P值〈0．01的差异多肽建立评价疗效的支持向量机（SVM）诊断模型，对AL患者与健康人进行区分，其敏感性及特异性分别为98％和99％；区分初治患者与达到血液学缓解（AL—HCR）患者的敏感性和特异性分别为98％和96％；区分AL-HCR患者与分子学缓解（AL-MR）患者的敏感性及特异性分别为92％和93％。与健康对照组相比，质荷比（m／z）为4468的多肽在初治AL患者中表达明显增高，随着治疗后缓解程度的加深强度逐渐下调，在良性血液病患者中表达未见升高。结论利用血清多肽图表达的差异多肽建立SVM诊断模型可以对AL患者不同缓解程度进行区分，用于临床疗效的评价。其中多肽m／z 4468可用于AL患者MRD的检测，连续监测其表达水平对个体化治疗及预测复发有重要意义。

英文摘要：

Objective To screen serum biomarkers for minimal residual disease （MRD） monitoring according to differential peptidomic profile in the serum from the patients with acute leukemia （AL） and healthy controls. Methods Serum polypeptides from 90 AL patients, 60 healthy controls and 20 patients with benign hematological disorders were enriched by copper chelate magnetic beads, and the peptidomic profile was obtained by matrix assisted laser desorption ionization time of flight mass spectrometry （MALDI-TOF-MS） analysis. And the intensities of differential peptides were calculated to assess MRD level. Results The diagnostic models by using support vector machine （SVM） algorithm according to differential peptides between AL patients and healthy controls with P〈0.01 by t-test were established. The sensitivity and specificity of distinguishing AL patients from healthy controls were 98% and 99%, respectively. The model obtained a sensitivity of 98% and a specificity of 96% for distinguishing newly-diagnosed AL patients from AL patients with hematological complete remission （AL-HCR）. Then a sensitivity of 92% and a specificity of 93% were obtained for distinguishing patients with AL-CR from AL patients with molecular complete remission （AL-MR）. The intensity of peptide with m/z （mass-to-charge ratio） 4468 was significantly higher in newly-diagnosed AL patients compared to healthy controls, and gradually decreased with the increase of remission degree, and it was not found increase in patients with benign hematological disorders. Conclusion The SVM diagnostic model established by differential serum peptide profile could be used to discriminate AL patients with different stages of remission and to evaluate the treatment efficacy. The peptide of m/z 4468 could be used for MRD assessment, and continuous monitoring of its expression level will play an important role in the individual treatment and recurrence prediction.