title: Fast apoptosis and erythroid differentiation induced by imatinib mesylate in JURL-MK1 cells.
abstract: We compare the effects of Imatinib mesylate (Glivec) on chronic myeloid leukemia derived cell lines K562 and JURL-MK1. In both cell lines, the cell cycle arrests in G(1)/G(0) phase within 24 h after the addition of 1 microM Imatinib. This is followed by a decrease of Ki-67 expression and the induction of apoptosis. In JURL-MK1 cells, the apoptosis is faster in comparison with K562 cells: the caspase-3 activity reaches the peak value (20 to 30 fold of the control) after about 40 h and the apoptosis proceeds to its culmination point, the DNA fragmentation, within 48 h following 1 microM Imatinib addition. Unlike K562 cells, JURL-MK1 cells possess a probably functional p53 protein inducible by TPA (tetradecanoyl phorbol acetate) or UV-B irradiation. However, no increase in p53 expression was observed in Imatinib-treated JURL-MK1 cells indicating that the difference in the apoptosis rate between the two cell lines is not due to the lack of p53 in K562 cells. Imatinib also triggers erythroid differentiation both in JURL-MK1 and K562 cells. Glycophorin A expression occurred simultaneously with the apoptosis, even at the single cell level. In K562 cells, but not in JURL-MK1 cells, the differentiation process involved increased hemoglobin synthesis. However, during spontaneous evolution of JURL-MK1 cells in culture, the effects produced by Imatinib progressively changed from the fast apoptosis to the more complete erythroid differentiation. We suggest that the apoptosis and the erythroid differentiation are parallel effects of Imatinib and their relative contributions, kinetics and completeness are related to the differentiation stage of the treated cells.
authors.affiliation: Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic. kuzel@uhkt.cz
authors.forename: Katerina
authors.initials: K
authors.lastname: Kuzelová
authors.forename: Dana
authors.initials: D
authors.lastname: Grebenová
authors.forename: Iuri
authors.initials: I
authors.lastname: Marinov
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Hrkal
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002463:Cell Membrane Permeability; D004789:Enzyme Activation; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006021:Glycophorins / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D019394:Ki-67 Antigen / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D006021:Glycophorins; D019394:Ki-67 Antigen; D010879:Piperazines; D011743:Pyrimidines; D016159:Tumor Suppressor Protein p53; D000068877:Imatinib Mesylate