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Updated: Mar 7, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Proteome Changes Induced by Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells
Katerina Arvaniti1, Anastasia Papadioti2, Maria Kinigopoulou3
1Division of Biochemistry, Department of Chemistry, University of Crete, P.O. Box 2208, GR-71003 Voutes, Greece. katarv87@gmail.com.
Abstract:
Imatinib mesylate is the leading compound to treat chronic myeloid leukemia (CML) and other cancers, through its inhibition of Bcr-Abl tyrosine kinases. However, resistance to imatinib develops frequently, particularly in late-stage disease and has necessitated the development of new Bcr-Abl inhibitors. The synthesis of a new series of phenylaminopyrimidines, structurally related to imatinib, showed large interest since the introduction of nilotinib. Here, we compare the protein levels in K562 cells treated with either imatinib or with novel imatinib derivates. Our results revealed that among the 986 quantified proteins, 35 had significantly altered levels of expression by imatinib or its derivates. In a second series of experiments, we directly compared the proteomes of imatinib treated K562 cells with those K562 cells treated with any of the four imatinib derivates. More than 1029 protein were quantified, 80 of which had altered levels of expression. Both experiments pointed to changes in the expression of the ATP-dependent RNA helicase DDX3X and of two mitochondrial coiled-coil-helix-coiled-coil-helix domain-containing proteins.
Insights
New imatinib derivatives show promise for treating chronic myeloid leukemia (CML). Proteomic analysis revealed altered protein expression, including DDX3X and mitochondrial proteins, in response to these novel compounds.
Area of Science:
- Biochemistry
- Oncology
- Proteomics
Background:
- Imatinib mesylate is a primary treatment for chronic myeloid leukemia (CML) by inhibiting Bcr-Abl tyrosine kinases.
- Acquired resistance to imatinib is a significant challenge, driving the need for novel therapeutic agents.
- Phenylaminopyrimidine derivatives, similar to imatinib and nilotinib, represent a promising class of new Bcr-Abl inhibitors.
Purpose of the Study:
- To compare the proteomic changes induced by imatinib and novel imatinib derivatives in K562 cells.
- To identify specific proteins whose expression levels are altered by these compounds.
- To evaluate the potential of new imatinib derivatives as alternative or supplementary treatments for CML.
Main Methods:
- Quantitative proteomic analysis of K562 cells treated with imatinib and novel imatinib derivatives.
- Mass spectrometry-based protein quantification to identify differentially expressed proteins.
- Comparative proteome analysis to assess the impact of different Bcr-Abl inhibitors.
Main Results:
- In the first experiment, 35 out of 986 quantified proteins showed significantly altered expression levels upon treatment with imatinib or its derivatives.
- In the second experiment, 80 out of 1029 quantified proteins exhibited altered expression when comparing imatinib-treated cells to cells treated with novel derivatives.
- Both experimental approaches indicated significant changes in the expression of ATP-dependent RNA helicase DDX3X and two mitochondrial coiled-coil-helix-coiled-coil-helix domain-containing proteins.
Conclusions:
- Novel imatinib derivatives induce distinct proteomic alterations compared to imatinib.
- DDX3X and specific mitochondrial proteins are potential biomarkers for drug response or resistance.
- These findings support the further investigation of imatinib derivatives for CML treatment.
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