, Volume 6, Issue 4, pp 383-388

Characterization of cancer stem-like cells in a novel STI571-resistant chronic myeloid leukemia cell line

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Abstract

Objective

To characterize a novel chronic myeloid leukemia (CML) cell line and to further elucidate the mechanisms of resistance to STI571.

Methods

A novel K562 cell line (K562/VP16) was achieved after exposure of the K562 cells to VP16. A small subpopulation (K562/VP16 SP) that was capable of excluding Hoechst 33342 in the K562/VP16 cell line was isolated by flow cytometry sorting. The rest of the K562/VP16 cells were classified as non-SP K562/VP16. The mechanisms involved in K562/VP16 SP cells which became resistant to STI571 were studied.

Results

The levels of Bcr-Abl and Abl proteins were similar in the K562 cell line and in non-SP K562/VP16 and K562/VP16 SP cells. The multidrug-resistant gene 1 (MDR1) expression of the 170 kDa P-glycoprotein (P-gp) was detected in K562/VP16 non-SP and K562/VP16 SP cells but not in K562 cells. The expression levels of P-gp in the two K562/VP16 cell lines were similar. Compared with non-SP K562/VP16, the K562/VP16 SP cells were more resistant to STI571. This resistance could hardly be reversed by many multidrug resistance inhibitors. In addition, in vivo study showed that the K562/VP16 SP cells induced tumorigenesis in mice, while the K562/VP16 non-SP cells failed to do so.

Conclusion

A novel K562 cell line, K562/VP16, was generated. A small side population K562/VP16 SP cells, had high resistance to STI571 treatment and more tumorigenic than the K562 cells. It may represent the cancer stem cells of the K562/VP16 cell line.

Supported by grants from National Development Plan of High Technology 863 (No. 2002AA205061) and Henan Outstanding Youth Foundation (No. 0612000900).