SphK-1/S1P signal pathway in CML cells.
- Author:
Wen-Rong HUANG
1
;
Li-Sheng WANG
;
Hua WANG
;
Hai-Feng DUAN
;
Qing-Fang LI
;
Chun-Ji GAO
;
Wan-Ming DA
Author Information
1. Department of Hematology, PLA General Hospital, Beijing 100853, China.
- Publication Type:Journal Article
- MeSH:
Benzamides;
Fusion Proteins, bcr-abl;
genetics;
metabolism;
Humans;
Imatinib Mesylate;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive;
genetics;
metabolism;
Lysophospholipids;
genetics;
metabolism;
Phosphotransferases (Alcohol Group Acceptor);
genetics;
metabolism;
Piperazines;
pharmacology;
Pyrimidines;
pharmacology;
RNA, Messenger;
genetics;
metabolism;
Signal Transduction;
genetics;
Sphingosine;
analogs & derivatives;
genetics;
metabolism
- From:
Journal of Experimental Hematology
2008;16(4):730-733
- CountryChina
- Language:Chinese
-
Abstract:
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. In order to investigate the role of sphingosine kinase-1 (SphK-1)/sphingosine 1-phosphate (S1P) signal pathway in the expression of CML cells, and to explore whether P210(bcr/abl) involved is activating SphK-1/S1P signal pathwey, the expressions of SphK-1 and S1P receptor mRNA in bcr/abl positive K562 cells and bcr/abl positive primary CML cells were detected by RT-PCR, the imatinib mesylate, the specific inhibitor of P210(bcr/abl) was employed to inhibit the P210(bcr/abl) tyrosine kinases of K562 cells and CML primary cells, and then the intracellular SphK-1 activity was assayed. The results indicated that after being cultured with 2.5 micromol/L imatinib mesylate for 0.5, 2, 6, 24 and 48 hours, the intensions of inhibiting SphK-1 activity were 0.007%, 38.9%, 34.6%, 28.1% and 76.1% resepectively. SphK-1 activity in CML cells also was reduced by 2.5 micromol/L imatinib mesylate (16.8% - 41.9% decrease). It is concluded that the CML cells express SphK-1 and different S1P receptor, and P210(bcr/abl) fusion protein in CML cells can activate SphK-1.
