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http://dx.doi.org/10.5352/JLS.2013.23.2.197

Presence of Leukemia-maintaining Cells in Differentiation-resistant Fraction of K562 Chronic Myelogenous Leukemia  

Lee, Hong-Rae (Department of Biochemistry, Pusan National University School of Medicine)
Kim, Mi-Ju (Department of Biochemistry, Pusan National University School of Medicine)
Ha, Gahee (Department of Biochemistry, Pusan National University School of Medicine)
Kim, So-Jung (MD-PhD program, Pusan National University School of Medicine)
Kim, Sun-Hee (Department of Biochemistry, Pusan National University School of Medicine)
Kang, Chi-Dug (Department of Biochemistry, Pusan National University School of Medicine)
Publication Information
Journal of Life Science / v.23, no.2, 2013 , pp. 197-206 More about this Journal
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.
Keywords
Chronic myelogenous leukemia; differentiation-resistance; imatinib; leukemia-maintaining cells; phorbol-12-myristate-13-acetate;
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