Differential tyrosine phosphorylation of leukemic cells during apoptosis as a result of treatment with imatinib mesylate.
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.
Park
Jungeun
J
Division of Molecular Genomic Medicine, College of Medicine, Seoul National University, Yongon-Dong, Seoul 110-799, Republic of Korea.
Kim
Sangmi
S
Oh
Chongkil
C
Yoon
Sung Soo
SS
Lee
Dongsoon
D
Kim
Youngsoo
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001549:Benzamides; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020543:Proteome / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D018797:Cell Cycle Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D020543:Proteome; D011743:Pyrimidines; C406060:abl-bcr fusion protein, human; D014443:Tyrosine; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl