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Single-cell analysis of K562 cells: An imatinib-resistant subpopulation is adherent and has upregulated expression of BCR-ABL mRNA and protein

Authors
  • Karimiani, Ehsan Ghayoor
  • Marriage, Fiona
  • Merritt, Anita J.
  • Burthem, John
  • Byers, Richard John
  • Day, Philip J.R.1, 2, 3, 4, 5, 6, 7, 5, 6, 8, 2, 9
  • 1 Institute of Cancer Sciences
  • 2 Faculty of Medical and Human Sciences
  • 3 University of Manchester, and Manchester Academic Health Science Centre
  • 4 Department of Histopathology
  • 5 Manchester Royal Infirmary
  • 6 Central Manchester University Hospitals NHS Foundation Trust
  • 7 Department of Hematology
  • 8 Quantitative Molecular Medicine Research Group
  • 9 University of Manchester
Type
Published Article
Journal
Experimental Hematology
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Nov 10, 2013
Volume
42
Issue
3
Pages
183–191
Identifiers
DOI: 10.1016/j.exphem.2013.11.006
Source
Elsevier
License
Unknown

Abstract

In chronic myeloid leukemia (CML) cells from different stages of maturation may have differential expression of BCR-ABL at both messenger RNA (mRNA) and protein level. However, the significance of such differential expression to clinical disease behavior is unknown. Using the CML-derived, BCR-ABL expressing cell line, K562, distinct plastic-adherent (K562/Adh) and nonadherent (K562/NonAdh) subpopulations were established and then analyzed both as single cells and as bulk cell populations. BCR-ABL mRNA was upregulated in K562/Adh compared with K562/NonAdh cells in both single cell and bulk population analyses (p < 0.0001). Similarly, phosphorylation of BCR protein was upregulated in K562/Adh, compared with K562/NonAdh cells (63.42% vs. 23.1%; p = 0.007), and these two K562 subpopulations were found to express significantly different microRNA species. Furthermore, treatment with the BCR-ABL tyrosine kinase inhibitor, imatinib, reduced cell viability more rapidly in K562/NonAdh compared with K562/Adh cells (p < 0.005) both at single and bulk cell levels. This discovery of an adherent subpopulation of K562 cells with increased BCR-ABL mRNA, increased phosphorylated BCR protein expression, differential microRNA expression, and increased imatinib resistance suggests that a similar subpopulation of cells can also mediate clinical resistance to imatinib during treatment of patients with CML.

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