title: p21(Cip1) confers resistance to imatinib in human chronic myeloid leukemia cells.
abstract: 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.
authors.affiliation: Departamento de Biología Molecular, Facultad de Medicina, Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria-CSIC-IDICAN, Santander, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Ferrandiz
authors.forename: Juan M
authors.initials: JM
authors.lastname: Caraballo
authors.forename: Marta
authors.initials: M
authors.lastname: Albajar
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Gomez-Casares
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Lopez-Jorge
authors.forename: Rosa
authors.initials: R
authors.lastname: Blanco
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Delgado
authors.forename: Javier
authors.initials: J
authors.lastname: Leon
mesh_terms: 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*
chemical_list: D001549:Benzamides; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate