A Proteomic Approach to Understand the Clinical Significance of Acute Myeloid Leukemia–Derived Extracellular Vesicles Reflecting Essential Characteristics of Leukemia

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. [Display omitted] •AML-derived EVs are key cargo proteins carrying parental AML cell information.•Proteomics of AML-derived EVs identify biomarkers predicting therapeutic responses.•EVs' CD53 and CD47 expression levels may be related to the prognosis of AML patients. We analyzed proteomics of AML cell–derived extracellular vesicles (EVs) that carry key information of parental cells. CD53 and CD47 were selected as predictive EV markers for AML, which showed good correlation with relapse-free survival of patients. In addition, several tyrosine kinases were enriched in AML cell–derived EVs, which may serve as potential therapeutic targets for AML.