Inhibition of XXXX induces apoptosis and decreases anaplastic lymphoma kinase activity in @entity2108 .

@entity7041 @entity22943 @entity522 @entity588 @entity4104 @entity1836 @entity18923 @entity2108 @entity7803 @entity669 @entity994
@entity4104 ( @entity4104 ), normally activated by Janus kinase (JAK) in response to cytokine stimulation, has been shown to have oncogenic potential. In addition to JAK, recent data suggest that @entity4104 can also be activated by other proteins such as the aberrant fusion protein, NPM- @entity7041 , which is expressed in a subset of @entity2108 ( @entity2108 ). In this study, we investigated the possible role of JAK in activating @entity4104 in @entity2108 using two @entity7041 -positive @entity2108 cell lines, Karpas 299 and SU-DHL-1. At the steady state, @entity7803 showed detectable @entity669 phosphorylation by immunoprecipitation. Treatment with @entity22943 , a JAK inhibitor, decreased but did not completely abrogate @entity669 phosphorylation of @entity7803 and @entity4104 in a concentration-dependent manner. Similar results were obtained using two other inhibitors of @entity7803 , WHI-P131 and WHI-P154. These biochemical changes were associated with apoptosis in both cell lines that was coupled with activation of @entity522 and decreased @entity1836 and @entity588 . Cell cycle analysis revealed a decrease in the S phase, which may be attributed to @entity18923 downregulation and @entity994 ) upregulation. Importantly, the @entity669 kinase activity of NPM- @entity7041 , as assessed by an in vitro assay, decreased with increasing concentrations of @entity22943 . Our findings highlight the importance of @entity7803 in activating @entity4104 in @entity2108 , and that NPM- @entity7041 -mediated activation of @entity4104 is influenced by the functional status of @entity7803 .
