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

Autor: Kwang Pyo Kim, Jik Han Jung, Hyesun Jeong, Yong Park, Ji-Ho Park, Kil Yeon Lee, Hyunku Shin, Sunghoi Hong, Byeong Hyeon Choi, Ka Won Kang, Dongkwon Seo, Hyun Koo Kim, Woojune Hur, Hyoseon Kim, Yeonho Choi, Su Jin Jeong
Rok vydání: 2021
Předmět:
Proteomics
Male
Syk
Biochemistry
Analytical Chemistry
hemic and lymphatic diseases
AML
acute myeloid leukemia
Cells
Cultured
DLS
dynamic light scattering
0303 health sciences
LC-MS/MS
liquid chromatography–tandem mass spectrometry
Kinase
030302 biochemistry & molecular biology
Myeloid leukemia
Extracellular vesicle
Middle Aged
Leukemia
Myeloid
Acute
Leukemia
medicine.anatomical_structure
DEPs
differentially expressed proteins
Female
Adult
FDR
false discovery rate
Adolescent
Biology
Extracellular Vesicles
Young Adult
03 medical and health sciences
FBS
fetal bovine serum
EV
extracellular vesicle
Antigens
CD
LYN
RFS
relapse-free survival
Biomarkers
Tumor
medicine
Humans
TEM
transmission electron microscopy
Molecular Biology
Aged
030304 developmental biology
Acute myeloid leukemia
Research
TMT
tandem mass tag
ACN
acetonitrile
CR
complete remission
FC
fold change
medicine.disease
HR
hazard ratio
LC-MS
CI
confidence interval
BM
bone marrow
Cancer research
TCGA
The Cancer Genome Atlas
Bone marrow
FPKM
fragments per kilobase of transcript per million
hMSCs
human mesenchymal stem cells
Protein Kinases
HDFa
human dermal fibroblasts
adult
Zdroj: Molecular & Cellular Proteomics : MCP
ISSN: 1535-9476
DOI: 10.1074/mcp.ra120.002169
Popis: 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.
Graphical Abstract
Highlights • 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.
In Brief 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.
Databáze: OpenAIRE
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