PXD019283-1

PXD019283 is an original dataset announced via ProteomeXchange.

Title	Exosomes released by imatinib-resistant K562 cells carry specific membrane markers and increase survival of imatinib-sensitive cells in the presence of imatinib.
Description	Chronic myeloid leukemia is a malignant hematopoietic disorder distinguished by a presence of BCR-ABL fused oncogene with constitutive kinase activity. Although targeted therapy by tyrosine kinase inhibitors (TKI) markedly improved patient´s survival and quality of life, development of drug resistance remains a critical issue for a subset of patients. The most common mechanism of TKI resistance in CML patients is a mutation in BCR-ABL gene which makes oncogenic Bcr-Abl protein insensitive to TKI therapy. Mutation independent mechanisms of TKI resistance are less elucidated, but exosomes, extracellular vesicles excreted from normal and tumor cells were recently linked with cancer progression and drug resistance. We used an imatinib-sensitive CML cell line K562 and derived an imatinib-resistant subline K562IR by prolonged cultivation of cells in presence of imatinib. We demonstrated that exosomes isolated from K562IR cells are internalized by K562 cells and increase their survival in presence of 2µM imatinib. To characterize the exosomal cargo and to identify resistance-associated marker proteins, we performed a deep proteomic analysis of exosomes from both cell sublines using label free quantification (LFQ). In total, we identified over 3000 exosomal proteins including 31 proteins differentially abundant in exosomes derived from K562IR cells. Among the differential proteins were three massively upregulated membrane proteins in K562IR exosomes with surface localization: IFITM3, CD146, CD36. We verified the massive upregulation of the three proteins in K562IR exosomes and also in K562IR cells. Using flow cytometry, we further demonstrated potential of CD146 as cell surface marker associated with imatinib resistance in K562 cells.
HostingRepository	PRIDE
AnnounceDate	2024-10-24
AnnouncementXML	Submission_2024-10-24_11:26:42.397.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jiri DRESLER
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-18 21:49:31	ID requested
⏵ 1	2024-10-24 11:26:42	announced

10.3892/IJO.2020.5163;

submitter keyword: chronic myeloid leukemia ,human cell lines, imatinib, LC-MS/MS

Jiri Dresler
contact affiliation	Military Health Institute, Prague, Czech Republic
contact email	jiri.dresler@gmail.com
lab head
Jiri DRESLER
contact affiliation	Military Health Institute, Prague/Czech Republic
contact email	jiri.dresler@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019283
     1. Label: PRIDE project
     2. Name: Exosomes released by imatinib-resistant K562 cells carry specific membrane markers and increase survival of imatinib-sensitive cells in the presence of imatinib.