Apoptotic effect of fludarabine is independent of expression of IAPs in B-cell chronic lymphocytic leukemia

Apoptosis : an International Journal on Programmed Cell Death
Karina L SilvaR C Maia

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.

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Citations

Mar 13, 2008·Cancer Chemotherapy and Pharmacology·Karina Lani SilvaRaquel Ciuvalschi Maia
Feb 2, 2012·Nature Reviews. Drug Discovery·Simone Fulda, Domagoj Vucic
Dec 2, 2011·Journal of Cancer Research and Clinical Oncology·Ana Carolina Dos Santos FerreiraClaudete Esteves Klumb
Apr 27, 2013·Leukemia Research·Cinzia ScavulloGiorgio Lambertenghi Deliliers
Jan 5, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Olga Grzybowska-IzydorczykPiotr Smolewski
Jun 23, 2015·International Journal of Cancer. Journal International Du Cancer·Daniela OpelSimone Fulda
Jul 31, 2013·Leukemia Research·Karina Lani SilvaRaquel Ciuvalschi Maia
Nov 19, 2009·Cancer Research·Sandra LoederSimone Fulda

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