eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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1/2011
vol. 36
 
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abstract:

Clinical immunology
Induction of apoptosis in B-CLL cells by selected histone deacetylase inhibitors

Joanna Kolano
,
Dorota Koczkodaj
,
Agata Filip
,
Bogumiła Ciseł
,
Jacek Wojcierowski
,
Ewa Wąsik
,
Anna Dmoszyńska
,
Witalis Misiewicz

(Centr Eur J Immunol 2011; 36 (1): 24-32)
Online publish date: 2011/03/31
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Histone modifications influence the chromatin structure, changing the patterns of gene expression. Histone deacetylases (HDACs) comprise a group of enzymes governing acetylation status of N-terminal lysine residues of four core histones. Acetylation, the result of histone deacetylases inhibition, leads to cell cycle arrest and differentiation or apoptosis in neoplastic cells. The aim of the study was to induce apoptosis in B-cell chronic lymphocytic leukemia cells in vitro using histone deacetylase inhibitors. B-CLL cells isolated from peripheral blood of 30 patients were examined after 24 hour culture with histone deacetylase inhibitors: phenylbutyric acid and sodium butyrate. Control B-CLL cells were cultured either with dexamethasone (positive control of apoptosis) or media alone (negative control of apoptosis). Normal cells were also examined in this study: 6 specimens of B-lymphocytes isolated from tonsils and 6 specimens of peripheral blood lymphocytes isolated from healthy blood donors. All samples were treated in identical conditions. The number of apoptotic cells was assessed in a flow cytometer (BD FACScalibur) with the use of active caspase-3 apoptosis kit. Expression of P21 and HDAC1 genes was analysed using RT-PCR technique and compared to GAPDH gene expression. The level of histone H3 and H4 acetylation was determined with Western-blot analysis. Histone deacetylase inhibitors used in this study (phenylbutyric acid and sodium butyrate) induced apoptosis in B-CLL. In the cells treated with HDAC inhibitors the level of acetylated histones H3 and H4 increase along with P21 gene expression. These findings may be applied in future in vivo tests inducing apoptosis of neoplastic cells in patients with chronic lymphocytic leukemia.
keywords:

histone deacetylases (HDACs), phenylbutyric acid, sodium butyrate, apoptosis, B-CLL

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