Differential effects of CXCR4 antagonists on the survival and proliferation of myeloid leukemia cells in vitro.
10.5045/kjh.2011.46.4.244
- Author:
Ha Yon KIM
1
;
Ji Young HWANG
;
Yoon Suk OH
;
Seong Woo KIM
;
Hyo Jin LEE
;
Hwan Jung YUN
;
Samyong KIM
;
Young Jun YANG
;
Deog Yeon JO
Author Information
1. Department of Medical Science, School of Medicine, Chungnam National University, Daejeon, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
AMD3100;
CXCR4;
SDF-1;
Myeloid leukemia;
Cell proliferation;
Apoptosis
- MeSH:
Annexin A5;
Apoptosis;
Cell Count;
Cell Line;
Cell Proliferation;
Flow Cytometry;
Hematopoietic Stem Cells;
Heterocyclic Compounds;
Humans;
Leukemia;
Leukemia, Myeloid;
Oligopeptides;
Pertussis Toxin;
Phosphorylation;
Receptors, CXCR4
- From:Korean Journal of Hematology
2011;46(4):244-252
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Antagonists of CXC chemokine receptor 4 (CXCR4), including AMD3100, induce peripheral mobilization of hematopoietic stem cells and have been approved for clinical use. We explored whether the CXCR4 antagonists affected the survival and proliferation of myeloid leukemia cells in vitro. METHODS: The effects of CXCR4 antagonists AMD3100 and T140 on the survival and proliferation of myeloid leukemia cell lines (U937, HL-60, MO7e, KG1a, and K562) as well as CD34+ cells obtained from patients with AML and CML were analyzed by flow cytometry by using annexin V and a colorimetric cell proliferation assay. RESULTS: AMD3100, but not T140, stimulated the proliferation of leukemia cells in vitro in a dose-dependent manner for up to 5 days (~2-fold increase at a concentration of 10-5 M), which was not abrogated by pretreatment of the cells with pertussis toxin, but was attenuated by RNAi knockdown of CXCR7 transcripts. In contrast, AMD3100 induced a marked decrease in the cell numbers after 5-7 days. AMD3100, but not T140, induced phosphorylation of MAPK p44/p42. AMD3100 increased the number and size of leukemia cell colonies and reduced cell apoptosis during the first 5-7 days of incubation, but the phenomena were reversed during the later period of incubation. CONCLUSION: The effects of CXCR4 antagonists on the proliferation of myeloid leukemia cells are not uniform. AMD3100, but not T140, exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of the cells in vitro.
