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Title: Targeting sphingosine kinase-1/spingosine-1-phosphate receptor 2 signalling pathway to overcome T315I mutation in 32DCL3 cells
Authors: Adan Gökbulut, Aysun
Öğretmen, Besim
Baran, Yusuf
Issue Date: 2014
Publisher: Elsevier Ltd.
Abstract: The main problem in chronic myeloid leukemia patients is the development of resistance against tyrosine kinase inhibitors. The expression of BCR-ABL1 having T315 mutation is responsible for the development of nilotinib resistance. The alterations in sphingolipid signalling pathway is a significant BCR-ABL1-dependent resistance mechanism. Recently, we showed that sphingosine kinase-1 (SK-1)/sphingosine-1 phosphate (S1P)-mediated drug resistance is transduced via sphingosine-1 phosphate receptor 2 (S1P2) that inhibits protein phosphatase 2A (PP2A), causing increased stability of BCR-ABL1. However, specific signaling cascade involved in this process remain unkown. In this study, BCR-ABL1 expressing 32Dcl3 cells, 32D-p210Bcr-Abl(wt) and 32D-p210Bcr-Abl (T315I) were used. The antiproliferative effects of nilotinib, SK-1 inhibitor (PF-543), S1P2 inhibitor (JTE-013), phospholipase C inhibitor (U-73122) and nilotinib/PF-543 and nilotinib/JTE-013 combinations on wt and resistant cells were determined by MTT assay. Isobologram analysis was performed using CompuSyn program.
Description: 5th International Eurasian Hematology Congress
ISSN: 0145-2126
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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