title: Imatinib increases apoptosis index through modulation of survivin subcellular localization in the blast phase of CML cells.
abstract: Using MTT, Annexin V/flow cytometry, immunocytochemistry, subcellular fractionation, and Western blotting assays we analyzed the effect of imatinib in two blast phase of chronic myeloid leukemia (CML) cell lines: K562 P-glycoprotein (Pgp)-negative, and Lucena, Pgp-positive. In K562 cell line, the high apoptosis index induced by imatinib was associated with the survivin predominantly in the nucleus. In the Lucena cell line, the low apoptosis index induced by imatinib was associated with a cytoplasmatic survivin localization. Pgp and survivin might be subject to the same molecular regulation, and therefore represent a therapeutic target in the blast phase of CML.
authors.affiliation: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro (RJ), Brazil.
authors.forename: Paula Sabbo
authors.initials: PS
authors.lastname: Bernardo
authors.forename: Flaviana Ruade de Souza
authors.initials: FR
authors.lastname: Reis
authors.forename: Raquel Ciuvalschi
authors.initials: RC
authors.lastname: Maia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D000077022:Survivin
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017304:Annexin A5; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D001549:Benzamides; D051034:Inhibitor of Apoptosis Proteins; D010879:Piperazines; D011743:Pyrimidines; D000077022:Survivin; D000068877:Imatinib Mesylate