Division of Hematology-Oncology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea.
Department of Applied Chemistry, Institute of Natural Science, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin, South Korea; Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul, South Korea.
Mol Cell Proteomics. 2021;20:100017. doi: 10.1074/mcp.RA120.002169. Epub 2020 Dec 8.
Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. ELISA results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML cell-derived EVs could reflect essential leukemia biology.
采用质谱分析法分析了急性髓系白血病 (AML) 细胞系的细胞外囊泡 (EV) 蛋白。分析鉴定出 2450 种蛋白质，其中包括 461 种差异表达蛋白（290 种上调和 171 种下调）。CD53 和 CD47 上调，被选为候选生物标志物。使用来自癌症基因组图谱 (TCGA) 数据库的 mRNA 表达数据，分析了 AML 患者的生存与诊断时 CD53 和 CD47 表达水平之间的关系。表达水平较高的患者的生存率明显低于表达水平较低的患者。对 AML 患者初诊时和诱导化疗完全缓解时骨髓 EVs 中 CD53 和 CD47 表达水平的 ELISA 结果表明，CD53 和 CD47 表达下调的患者似乎复发频率较低。EV 蛋白的网络模型分析显示了几种上调的激酶，包括 LYN、CSNK2A1、SYK、CSK 和 PTK2B。在 AML 细胞系中测试了几种抑制这些激酶的临床应用药物的潜在细胞毒性。这些药物降低了 AML 细胞的活力。综合数据表明，AML 细胞来源的 EV 可能反映了白血病的基本生物学特性。
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