Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia.

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Bruton's tyrosine kinase inhibitor restrains Wnt signaling in chronic lymphocytic leukemia.

Mol Med Rep. 2016 Jun;13(6):4934-8

Authors: Li PP, Lu K, Geng LY, Zhou XX, Li XY, Wang X

Abstract
The B-cell receptor (BCR) signaling pathway serves an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and has been identified as a novel and effective therapeutic target of CLL, with particular focus its kinase factor, BTK. Previous studies have focused on combining the BTK inhibitor with additional chemotherapeutic agents to improve the prognosis of patients with CLL. Further investigation into the mechanism of the BTK inhibitor would promote an understanding of the pathogenesis of CLL. The current study investigated the association between ibrutinib and the Wnt signaling pathway, additionally focussing upon one of its regulators, metadherin (MTDH), which has been identified to be overexpressed in CLL and is considered a promoter of the Wnt pathway. The experiments in the current study were performed in the MEC-1 CLL cell line. Results indicated that MTDH, β-catenin and lymphoid-enhancing factor-1 were inhibited subsequent to ibrutinib treatment. The results indicate that in CLL, ibrutinib is likely to possess an inhibitory role in Wnt signaling.

PMID: 27082823 [PubMed - indexed for MEDLINE]

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