KMID : 0613820130230020197
|
|
Journal of Life Science 2013 Volume.23 No. 2 p.197 ~ p.206
|
|
Presence of Leukemia-maintaining Cells in Differentiation-resistant Fraction of K562 Chronic Myelogenous Leukemia
|
|
Lee Hong-Rae
Kim Mi-Ju Ha Ga-hee Kim So-Jung Kim Sun-Hee Kang Chi-Dug
|
|
Abstract
|
|
|
The present study investigated whether leukemia-maintaining cells reside in a differentiation-resistant fraction using a megakaryocytic differentiation model of K562 cells. Treatment with phorbol-12-myristate-13-acetate (PMA) significantly inhibited the colony-forming efficiency of the K562 cells. At a PMA concentration of 1 nM or higher, colony was not formed, but approximately 40% of K562 cells still survived in soft agar. Approximately 70% of colony-forming cells that were isolated following the removal of PMA after exposure to the agent were differentiated after treatment with 10 nM PMA for 3 days. The differentiation rate of the colony-forming cells was gradually increased and reached about 90% 6 weeks after colony isolation, which was comparable to the level of a PMA-treated K562 control. Meanwhile, imatinib-resistant variants from the K562 cells, including K562/R1, K562/R2, and K562/R3 cells, did not show any colony-forming activity, and most imatinib-resistant variants were CD44 positive. After 4 months of culture in drug-free medium, the surface level of CD44 was decreased in comparison with primary imatinib-resistant variants, and a few colonies were formed from K562/R3 cells. In these cells, Bcr-Abl, which was lost in the imatinib-resistant variants, was re-expressed, and the original phenotypes of the K562 cells were partially recovered. These results suggest that leukemia-maintaining cells might reside in a differentiation-resistant population. Differentiation therapy to eliminate leukemia-maintaining cells could be a successful treatment for leukemia if the leukemia-maintaining cells were exposed to a differentiation inducer for a long time and at a high dose.
|
|
KEYWORD
|
|
Chronic myelogenous leukemia, differentiation-resistance, imatinib, leukemia-maintaining cells, phorbol-12-myristate-13-acetate
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|