title: Apoptotic effect of fludarabine is independent of expression of IAPs in B-cell chronic lymphocytic leukemia.
abstract: Despite the efficiency of fludarabine in the induction of clinical responses in B-cell chronic lymphocytic leukemia (B-CLL) patients, resistance to this drug has been documented. The present study tested whether resistance to fludarabine is related to the expression of inhibitor of apoptosis proteins (IAPs) family members. We analyzed the expression of c-IAP1, c-IAP2 and XIAP, by immunocytochemistry, in 30 blood samples from B-CLL patients and correlated protein expression to fludarabine-induced apoptosis estimated by an annexin-V assay. Expression of c-IAP1, c-IAP2 and XIAP were found predominantly in the cytoplasm, and a wide range of staining intensities was observed among distinct samples. No correlation was found between the levels of IAPs expression and prognostic factors such as age, gender, lymphocyte doubling time, white blood cell count or previous treatment. The expression of IAPs also failed to predict the sensitivity to fludarabine-induced apoptosis. Alternative pathways of cell death may explain the independence of fludarabine-induced apoptosis from the high expression of IAPs.
authors.affiliation: Laboratório de Hematologia Celular e Molecular, Serviço de Hematologia, Hospital do Câncer I, Instituto Nacional de Câncer, Rio de Janeiro, Brasil.
authors.forename: K L
authors.initials: KL
authors.lastname: Silva
authors.forename: D V
authors.initials: DV
authors.lastname: Vasconcellos
authors.forename: E D de Paula
authors.initials: ED
authors.lastname: Castro
authors.forename: A M
authors.initials: AM
authors.lastname: Coelho
authors.forename: R
authors.initials: R
authors.lastname: Linden
authors.forename: R C
authors.initials: RC
authors.lastname: Maia
mesh_terms: D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D017304:Annexin A5; D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D014740:Vidarabine; C024352:fludarabine