title: Proteome Changes Induced by Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells.
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.
authors.affiliation: Division of Biochemistry, Department of Chemistry, University of Crete, P.O. Box 2208, GR-71003 Voutes, Greece. katarv87@gmail.com.
authors.forename: Katerina
authors.initials: K
authors.lastname: Arvaniti
authors.affiliation: Division of Biochemistry, Department of Chemistry, University of Crete, P.O. Box 2208, GR-71003 Voutes, Greece. anastasia_papadioti@hotmail.com.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Papadioti
authors.affiliation: Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece. m_kinigopoulou@hotmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Kinigopoulou
authors.affiliation: Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece. vtheodor@cc.uoi.gr.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Theodorou
authors.affiliation: Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece. kskobrid@cc.uoi.gr.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Skobridis
authors.affiliation: Division of Biochemistry, Department of Chemistry, University of Crete, P.O. Box 2208, GR-71003 Voutes, Greece. Tsiotis@chemistry.uoc.gr.
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsiotis
keywords: SILAC; chronic myeloid leukemia; imatinib; kinase inhibitors; protein kinases