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Differential tyrosine phosphorylation of leukemic cells during apoptosis as a result of treatment with imatinib mesylate

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Authors
Park, Jungeun; Kim, Sangmi; Oh, Chongkil; Yoon, Sung Soo; Lee, Dongsoon; Kim, Youngsoo
Issue Date
2005-09-15
Publisher
Academic Press
Citation
Biochem Biophys Res Commun. 2005 Oct 28;336(3):942-51.
Keywords
Antineoplastic Agents/*pharmacology*ApoptosisBlotting, WesternCell Cycle/drug effectsCell Cycle Proteins/genetics/metabolismCell Proliferation/drug effectsElectrophoresis, Gel, Two-DimensionalFusion Proteins, bcr-abl/*antagonists & inhibitorsHumansK562 CellsLeukemia, Myelogenous, Chronic, BCR-ABLPositive/*enzymology/metabolism/pathologyPhosphorylationPiperazines/*pharmacologyProtein Kinase Inhibitors/*pharmacologyProteome/metabolismPyrimidines/*pharmacologyTranscription, Genetic/drug effectsTyrosine/metabolism
Abstract
Bcr-Abl fusion tyrosine kinase contributes to leukemic transformation. Imatinib mesylate inhibits Bcr-Abl tyrosine kinase, resulting in a blockage of tyrosine phosphorylation in its downstream pathways. We analyzed the alteration of tyrosine phosphorylation, on BCR/ABL+ chronic myelogenous leukemia cells, after treatment with imatinib mesylate. Data were collected using a two-dimensional gel electrophoresis followed by Western blot and mass spectrometry. The inhibition of Bcr-Abl tyrosine kinase by 2.5 microM imatinib mesylate caused both cell cycle arrest in the G0/G1 phase and increased the portion of apoptotic cells. As a result, the population of leukemic cells decreased by 30% and 70% compared to controls at 24 and 72 h, respectively. Furthermore, treatment with imatinib mesylate altered tyrosine phosphorylation of 24 protein spots as the incubation time proceeded from 0 to 24 and 72 h. Ten of the 24 protein spots are visible at all three times. Four are detectable at both the 0 and 24 h points in time. Eight were detectable only at time 0.
ISSN
0006-291X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16157305

http://hdl.handle.net/10371/11564
DOI
https://doi.org/10.1016/j.bbrc.2005.08.201
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College of Medicine/School of Medicine (의과대학/대학원)Laboratory Medicine (검사의학전공)Journal Papers (저널논문_검사의학전공)
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