p21(Cip1) confers resistance to imatinib in human chronic myeloid leukemia cells.
Imatinib is a Bcr-Abl inhibitor used as first-line therapy of chronic myeloid leukemia (CML). p21(Cip1), initially described as a cell cycle inhibitor, also protects from apoptosis in some models. We describe that imatinib down-regulates p21(Cip1) expression in CML cells. Using K562 cells with inducible p21 expression and transient transfections we found that p21 confers partial resistance to imatinib-induced apoptosis. This protection is not related to the G2-arrest provoked by p21, a decrease in the imatinib activity against Bcr-Abl or a cytoplasmic localization of p21. The results suggest an involvement of p21(Cip1) in the response to imatinib in CML.
Ferrandiz
Nuria
N
Departamento de Biología Molecular, Facultad de Medicina, Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-CSIC-IDICAN, Santander, Spain.
Caraballo
Juan M
JM
Albajar
Marta
M
Gomez-Casares
M Teresa
MT
Lopez-Jorge
Carmen E
CE
Blanco
Rosa
R
Delgado
M Dolores
MD
Leon
Javier
J
D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D010879:Piperazines / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*
D001549:Benzamides; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate