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急性白血病蛋白质谱分类模型的构建及蛋白质组学特征筛选

Construction of protein profile classification model and screening of proteomic signature of acute leukemia.

作者信息

Xu Yun, Zhuo Jiacai, Duan Yonggang, Shi Benhang, Chen Xuhong, Zhang Xiaoli, Xiao Liang, Lou Jin, Huang Ruihong, Zhang Qiongli, Du Xin, Li Ming, Wang Daping, Shi Dunyun

机构信息

Central Laboratory, Shenzhen Second People's Hospital Shenzhen, Guangdong, China.

Institue of Hemotology, Shenzhen Second People's Hospital Shenzhen, Guangdong, China.

出版信息

Int J Clin Exp Pathol. 2014 Aug 15;7(9):5569-81. eCollection 2014.

Abstract

The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI_TOF_MS). The patients with acute leukemia were analyzed as unitary by the profiling that were grouped into acute promyelocytic leukemia (APL), acute myeloid leukemia-granulocytic (AML-Gran), acute myeloid leukemia-monocytic (AML-Mon) acute lymphocytic leukemia (ALL), and control. Based on 109 proteomic signatures, the classification models of acute leukemia were constructed to screen the predictors by the improvement of the proteomic signatures and to detect their expression characteristics. According to the improvement and the expression characteristics of the predictors, the proteomic signatures (M3829, M1593, M2121, M2536, M1016) characterized successively each group (CON, APL, AML-Gra, AML-Mon, ALL) were screened as target molecules for identification. Meanwhile, the proteomic-based class of determinant samples could be made by the classification models. The credibility of the proteomic-based classification passed the evaluation of Biomarker Patterns Software 5.0 (BPS 5.0) scoring and validated application in clinical practice. The results suggested that the proteomic signatures characterized by different blasts were potential for developing new treatment and monitoring approaches of leukemia blasts. Moreover, the classification model was potential in serving as new diagnose approach of leukemia.

摘要

法美英(FAB)分类法和世界卫生组织(WHO)分类法为急性白血病的诊断、治疗及预后预测提供了重要指导原则,但无法准确区分所有亚型,且与临床结果的相关性不佳。在本研究中,我们采用表面增强激光解吸/电离飞行时间质谱(SELDI_TOF_MS)对急性白血病患者及健康志愿者(对照)的骨髓单个核细胞进行了蛋白质谱分析。将急性白血病患者按谱图分析分为单一型,包括急性早幼粒细胞白血病(APL)、急性髓系白血病粒细胞型(AML-Gran)、急性髓系白血病单核细胞型(AML-Mon)、急性淋巴细胞白血病(ALL)及对照。基于109个蛋白质组学特征,构建急性白血病分类模型,通过改善蛋白质组学特征筛选预测指标,并检测其表达特征。根据预测指标的改善情况及表达特征,依次筛选出表征每组(对照、APL、AML-Gra、AML-Mon、ALL)的蛋白质组学特征(M3829、M1593、M2121、M2536、M1016)作为鉴定的靶分子。同时,可通过分类模型进行基于蛋白质组学的决定性样本分类。基于蛋白质组学的分类可信度通过生物标志物模式软件5.0(BPS 5.0)评分评估,并在临床实践中得到验证应用。结果表明,以不同原始细胞为特征的蛋白质组学特征在开发白血病原始细胞的新治疗和监测方法方面具有潜力。此外,该分类模型有望成为白血病的新诊断方法。

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