Characterization of K562 cells: uncovering novel chromosomes, assessing transferrin receptor expression, and probing pharmacological therapies

Tom C. Karagiannis, Meaghan Wall, Katherine Ververis, Eleni Pitsillou, Stephanie M. Tortorella, Peter A. Wood, Haloom Rafehi, Ishant Khurana, Scott S. Maxwell, Andrew Hung, Jitraporn Vongsvivut, Assam El-Osta

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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. Graphical abstract: [Figure not available: see fulltext.].

Original languageEnglish
Article number248
JournalCellular and Molecular Life Sciences
Volume80
Issue number9
ISSN1420-682X
DOIs
Publication statusPublished - Sept 2023

Keywords

  • BCR-ABL
  • Chronic myeloid leukemia
  • Doxorubicin
  • Histone deacetylase inhibitors
  • K562 cells
  • Philadelphia chromosome
  • Transferrin receptors

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