title: Predictability of the response to tyrosine kinase inhibitors via in vitro analysis of Bcr-Abl phosphorylation.
abstract: It would be of great value to predict the efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of individual CML patients. We propose an immunoblot system for detecting the phosphorylation of Crkl, a major target of Bcr-Abl, in blood samples after in vitro incubation with TKIs. When the remaining phosphorylated Crkl after treatment with imatinib was evaluated as the "residual index (RI)", high values were found in accordance with imatinib resistance. Moreover, RI reflected the outcome of imatinib- as well as second generation TKIs with a high sensitivity and specificity. Therefore, this system should be useful in the selection of TKIs.
authors: Hematology and Oncology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan.
authors: Masaru
authors: M
authors: Shibata
authors: Sachiko
authors: S
authors: Ezoe
authors: Kenji
authors: K
authors: Oritani
authors: Keiko
authors: K
authors: Matsui
authors: Masahiro
authors: M
authors: Tokunaga
authors: Natsuko
authors: N
authors: Fujita
authors: Yuri
authors: Y
authors: Saito
authors: Takayuki
authors: T
authors: Takahashi
authors: Masayuki
authors: M
authors: Hino
authors: Itaru
authors: I
authors: Matsumura
authors: Yuzuru
authors: Y
authors: Kanakura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; C082869:CRKL protein; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D016044:Fusion Proteins, bcr-abl