Imatinib increases apoptosis index through modulation of survivin subcellular localization in the blast phase of CML cells

• Published in: Leukemia research Vol. 36; no. 12; pp. 1510 - 1516
• Main Authors: Bernardo, Paula Sabbo, Reis, Flaviana Ruade de Souza, Maia, Raquel Ciuvalschi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2012
• Subjects: Annexin A5 - metabolism; Annexin V; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Benzamides; Blast; Blast Crisis - drug therapy; Blast Crisis - genetics; Blast Crisis - pathology; Blotting, Western; Cell Nucleus - metabolism; Cell Nucleus - pathology; Cell Survival - drug effects; Chronic myeloid leukemia; Cytoplasm - metabolism; Cytoplasm - pathology; Flow Cytometry; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Humans; Imatinib; Imatinib Mesylate; Immunocytochemistry; Immunohistochemistry; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Nuclei; P-Glycoprotein; Piperazines - pharmacology; Pyrimidines - pharmacology; Subcellular localization; Survivin; Tumor cell lines; Western blotting; P-glycoprotein; Imatinib; Chronic myeloid leukemia; Survivin; Subcellular localization
• ISSN: 0145-2126; 1873-5835; 1873-5835
• DOI: 10.1016/j.leukres.2012.08.014

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.