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- W2011887454 abstract "Diffuse large B cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma. While the initial treatment strategy is highly effective, relapse occurs in 40% of cases. Histone deacetylase inhibitors (HDACi) are a promising class of anti-cancer drugs but their single agent efficacy against relapsed DLBCL has been variable, ranging from few complete/partial responses to some stable disease. However, most patients showed no response to HDACi monotherapy for unknown reasons. Here we show that sensitivity and resistance to the hydroxamate HDACi, PXD101, can be modeled in DLBCL cell lines. Sensitivity is characterized by G 2/M arrest and apoptosis and resistance by reversible G 1 growth arrest. These responses to PXD101 are independent of several negative prognostic indicators such as DLBCL subtype, BCL2 and MYC co-expression, and p53 mutation, suggesting that HDACi might be used effectively against highly aggressive DLBCL tumors if they are combined with other therapeutics that overcome HDACi resistance. Our investigation of mechanisms underlying HDACi resistance showed that cyclin-dependent kinase inhibitors (CKIs), p21 and p27, are upregulated by PXD101 in a sustained fashion in resistant cell lines concomitant with decreased activity of the cyclin E/cdk2 complex and decreased Rb phosphorylation. PXD101 treatment results in increased association of CKI with the cyclin E/cdk2 complex in resistant cell lines but not in a sensitive line, indicating that the CKIs play a key role in G 1 arrest. The results suggest several treatment strategies that might increase the efficacy of HDACi against aggressive DLBCL." @default.
- W2011887454 created "2016-06-24" @default.
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- W2011887454 date "2013-10-05" @default.
- W2011887454 modified "2023-09-30" @default.
- W2011887454 title "A model of sensitivity and resistance to histone deacetylase inhibitors in diffuse large B cell lymphoma" @default.
- W2011887454 cites W1567485746 @default.
- W2011887454 cites W1602446144 @default.
- W2011887454 cites W1965837349 @default.
- W2011887454 cites W1971287536 @default.
- W2011887454 cites W1971659434 @default.
- W2011887454 cites W1976564639 @default.
- W2011887454 cites W1979104079 @default.
- W2011887454 cites W1983914017 @default.
- W2011887454 cites W1988466148 @default.
- W2011887454 cites W1991376723 @default.
- W2011887454 cites W1996105433 @default.
- W2011887454 cites W1996809397 @default.
- W2011887454 cites W2003262666 @default.
- W2011887454 cites W2008836678 @default.
- W2011887454 cites W2014350573 @default.
- W2011887454 cites W2018071905 @default.
- W2011887454 cites W2026004604 @default.
- W2011887454 cites W2027741880 @default.
- W2011887454 cites W2034042949 @default.
- W2011887454 cites W2038831537 @default.
- W2011887454 cites W2047542386 @default.
- W2011887454 cites W2047770089 @default.
- W2011887454 cites W2048743150 @default.
- W2011887454 cites W2056641238 @default.
- W2011887454 cites W2057358066 @default.
- W2011887454 cites W2062424910 @default.
- W2011887454 cites W2066264051 @default.
- W2011887454 cites W2067432529 @default.
- W2011887454 cites W2068751269 @default.
- W2011887454 cites W2069019880 @default.
- W2011887454 cites W2077522084 @default.
- W2011887454 cites W2095788199 @default.
- W2011887454 cites W2096596684 @default.
- W2011887454 cites W2097933346 @default.
- W2011887454 cites W2098155709 @default.
- W2011887454 cites W2098203835 @default.
- W2011887454 cites W2099013228 @default.
- W2011887454 cites W2107040737 @default.
- W2011887454 cites W2107808656 @default.
- W2011887454 cites W2110894784 @default.
- W2011887454 cites W2111155422 @default.
- W2011887454 cites W2114208687 @default.
- W2011887454 cites W2115354390 @default.
- W2011887454 cites W2117726013 @default.
- W2011887454 cites W2120376568 @default.
- W2011887454 cites W2123687793 @default.
- W2011887454 cites W2126425007 @default.
- W2011887454 cites W2130638154 @default.
- W2011887454 cites W2131724172 @default.
- W2011887454 cites W2135619784 @default.
- W2011887454 cites W2141920998 @default.
- W2011887454 cites W2147246240 @default.
- W2011887454 cites W2148800878 @default.
- W2011887454 cites W2151089955 @default.
- W2011887454 cites W2153183019 @default.
- W2011887454 cites W2153667947 @default.
- W2011887454 cites W2157575236 @default.
- W2011887454 cites W2159862107 @default.
- W2011887454 cites W2161004204 @default.
- W2011887454 cites W2163374595 @default.
- W2011887454 cites W2166529745 @default.
- W2011887454 cites W2167571754 @default.
- W2011887454 cites W2168946040 @default.
- W2011887454 cites W2169296145 @default.
- W2011887454 cites W2169508075 @default.
- W2011887454 cites W2317506706 @default.
- W2011887454 cites W292090967 @default.
- W2011887454 cites W296713146 @default.
- W2011887454 cites W31572314 @default.
- W2011887454 doi "https://doi.org/10.4161/cbt.25941" @default.
- W2011887454 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3926892" @default.
- W2011887454 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23982416" @default.
- W2011887454 hasPublicationYear "2013" @default.
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