Article

Predictability of the response to tyrosine kinase inhibitors via in vitro analysis of Bcr-Abl phosphorylation.

Hematology and Oncology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan.
Leukemia research (impact factor: 2.36). 03/2011; 35(9):1205-11. DOI:10.1016/j.leukres.2011.01.012 pp.1205-11
Source: PubMed

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.

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Keywords

Crkl
 
great value
 
individual CML patients
 
major target
 
remaining phosphorylated Crkl
 
residual index
 
second generation TKIs
 
TKIs
 
tyrosine kinase inhibitors
 
values
 
vitro incubation