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Silencing of APAF-1 in B-CLL results in poor prognosis in the case of concomitant p53 mutation

Item Type:Article
Title:Silencing of APAF-1 in B-CLL results in poor prognosis in the case of concomitant p53 mutation
Creators Name:Sturm, I., Bosanquet, A.G., Radetzki, S., Hummel, M., Doerken, B. and Daniel, P.T.
Abstract:Apoptosis protease-activating factor 1 (APAF-1), a transcriptional target of p53, is a cytosolic adaptor protein that links the mitochondrial apoptosis pathway to the caspase cascade. Here, we aimed to study the impact of APAF-1 expression levels on cell death induced by anticancer drugs or ionizing irradiation (IR) and disease prognosis in B-type chronic lymphocytic leukemia (B-CLL) patients. Samples from 138 patients with B-CLL were investigated for APAF-1 expression and p53 mutations. The results were related to survival data, in vitro cytotoxicity of various cytotoxic drugs and IR and clinico-pathological data. Variable APAF-1 expression was observed in all investigated B-CLL samples. Reduction in APAF-1 expression was observed at both mRNA and protein level indicating transcriptional silencing whereas mutation of p53 or the immunoglobulin heavy chain variable genes (IgHV) had no impact on APAF-1 expression. Surprisingly, APAF-1 loss did not result in resistance to cytotoxic therapies. Likewise, APAF-1 downregulation on its own showed no impact on disease prognosis. Nevertheless, a poor prognosis was observed in patients with loss of APAF-1 expression and additional p53 mutation. Thus, loss of APAF-1 may become relevant when additional core apoptosis signaling components are disrupted.
Keywords:APAF-1, p53 Mutation, Apoptosis, Drug sensitivity, B-CLL
Source:International Journal of Cancer
Page Range:2329-2336
Date:1 May 2006
Official Publication:https://doi.org/10.1002/ijc.21535
PubMed:View item in PubMed

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