Characterization of K562 cells: uncovering novel chromosomes, assessing transferrin receptor expression, and probing pharmacological therapies.
Humans
Imatinib Mesylate
/ pharmacology
K562 Cells
Fusion Proteins, bcr-abl
/ genetics
Transferrin
Pyrimidines
/ pharmacology
Drug Resistance, Neoplasm
/ genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ drug therapy
Histone Deacetylases
/ metabolism
Doxorubicin
/ pharmacology
Receptors, Transferrin
/ genetics
Chromosomes
/ metabolism
Mesylates
/ pharmacology
Apoptosis
BCR-ABL
Chronic myeloid leukemia
Doxorubicin
Histone deacetylase inhibitors
K562 cells
Philadelphia chromosome
Transferrin receptors
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
14 Aug 2023
14 Aug 2023
Historique:
received:
09
07
2023
accepted:
31
07
2023
revised:
30
07
2023
medline:
15
8
2023
pubmed:
14
8
2023
entrez:
14
8
2023
Statut:
epublish
Résumé
Human erythroleukemic K562 cells represent the prototypical cell culture model of chronic myeloid leukemia (CML). The cells are pseudo-triploid and positive for the Philadelphia chromosome. Therefore, K562 cells have been widely used for investigating the BCR/ABL1 oncogene and the tyrosine kinase inhibitor, imatinib-mesylate. Further, K562 cells overexpress transferrin receptors (TfR) and have been used as a model for targeting cytotoxic therapies, via receptor-mediated endocytosis. Here, we have characterized K562 cells focusing on the karyotype of cells in prolonged culture, regulation of expression of TfR in wildtype (WT) and doxorubicin-resistant cells, and responses to histone deacetylase inhibition (HDACi). Karyotype analysis indicates novel chromosomes and gene expression analysis suggests a shift of cultured K562 cells away from patient-derived leukemic cells. We confirm the high expression of TfR on K562 cells using immunofluorescence and cell-surface receptor binding radioassays. Importantly, high TfR expression is observed in patient-derived cells, and we highlight the persistent expression of TfR following doxorubicin acquired resistance. Epigenetic analysis indicates that permissive histone acetylation and methylation at the promoter region regulates the transcription of TfR in K562 cells. Finally, we show relatively high expression of HDAC enzymes in K562 cells and demonstrate the chemotoxic effects of HDACi, using the FDA-approved hydroxamic acid, vorinostat. Together with a description of morphology, infrared spectral analysis, and examination of metabolic properties, we provide a comprehensive characterization of K562 cells. Overall, K562 cell culture systems remain widely used for the investigation of novel therapeutics for CML, which is particularly important in cases of imatinib-mesylate resistance.
Identifiants
pubmed: 37578596
doi: 10.1007/s00018-023-04905-6
pii: 10.1007/s00018-023-04905-6
doi:
Substances chimiques
Imatinib Mesylate
8A1O1M485B
Fusion Proteins, bcr-abl
EC 2.7.10.2
Transferrin
0
Pyrimidines
0
Histone Deacetylases
EC 3.5.1.98
Doxorubicin
80168379AG
Receptors, Transferrin
0
Mesylates
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
248Informations de copyright
© 2023. Crown.
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