Huang Pauline Y, Mactier Swetlana, Armacki Natalie, Giles Best O, Belov Larissa, Kaufman Kimberley L, Pascovici Dana, Mulligan Stephen P, Christopherson Richard I
a School of Molecular Bioscience, University of Sydney , Sydney , NSW , Australia ;
b Northern Blood Research Centre, Kolling Institute of Medical Research, Royal North Shore Hospital , St. Leonards , NSW , Australia ;
Leuk Lymphoma. 2016 May;57(5):1033-43. doi: 10.3109/10428194.2015.1094692. Epub 2015 Nov 16.
Patients with a stable chronic lymphocytic leukemia (CLL) double their blood lymphocyte count in >5 years, but may develop progressive disease with lymphocytes doubling in <12 months. To identify a protein signature for progressive CLL, whole cell extracts of peripheral blood mononuclear cells from patients with CLL (n=27) were screened using iTRAQ (isobaric tags for relative and absolute quantification) analysis. A total of 84 differentially abundant proteins were identified from patients with stable and progressive CLL. Subsequently, 32 of these proteins were quantified by SRM (selected reaction monitoring) using extracts of purified CD19+ CLL cells from patients (n=50). Hierarchical clustering of these protein profiles showed two clusters of patients that correlated with progressive and stable CLL, providing signatures that should be useful for triaging patients. Some of the proteins in the progressive cluster have not been linked with CLL, for example, glutamate dehydrogenase 1 and transcription intermediary factor 1-beta.
患有稳定型慢性淋巴细胞白血病(CLL)的患者,其血液淋巴细胞计数在5年以上翻倍,但可能会发展为进展性疾病,淋巴细胞在12个月内翻倍。为了确定进展性CLL的蛋白质特征,使用iTRAQ(相对和绝对定量的等压标签)分析对CLL患者(n = 27)外周血单个核细胞的全细胞提取物进行筛选。从稳定型和进展型CLL患者中总共鉴定出84种差异丰富的蛋白质。随后,使用来自患者(n = 50)的纯化CD19 + CLL细胞提取物,通过SRM(选择反应监测)对其中32种蛋白质进行定量。这些蛋白质谱的层次聚类显示出与进展性和稳定型CLL相关的两组患者,提供了对患者进行分类应有用的特征。进展性聚类中的一些蛋白质尚未与CLL相关联,例如谷氨酸脱氢酶1和转录中介因子1-β。