Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2015, vol. 24, nr 1, January-February, p. 55–62

doi: 10.17219/acem/29264

Publication type: original article

Language: English

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Cytotoxic Activity of Valproic Acid on Primary Chronic Lymphocytic Leukemia Cells

Marta Karp1,B,C,D,F, Kamila Kosior2,B,C,D, Agnieszka Karczmarczyk1,D,E,F, Małgorzata Zając1,D,E,F, Joanna Zaleska1,D,E,F, Waldemar Tomczak2,D,E,F, Sylwia Chocholska2,D,E,F, Marek Hus2,D,E,F, Anna Dmoszyńska2,D,E,F, Krzysztof Giannopoulos1,2,A,B,C,D,E,F

1 Department of Experimental Hematooncology, Medical University of Lublin, Poland

2 Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Poland

Abstract

Background. Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in western civilization. The accumulation of CD5+CD19+ B lymphocytes in peripheral blood is due to a defect in the apoptotic pathway rather than excessive proliferation in the bone marrow and lymph nodes. Despite a number of treatments, CLL remains an incurable disease. Valproic acid (VPA) activity, as a histone deacetylase inhibitor, could restore the epigenetic changes underlying the pathogenesis of CLL and thus induce cell death.
Objectives. In the present study we hypothesized that VPA could induce CLL primary cells death through activation of apoptosis.
Material and Methods. Peripheral blood samples were obtained from 53 CLL patients. Peripheral blood mononuclear cells were isolated through density gradient centrifugation and were the subject of a 24-hour cell culture with 10 mM of VPA. The cytotoxic effect of VPA was evaluated with an XTT test and thereafter confirmed using Annexin V-FITC/PI staining and flow cytometry techniques.
Results. In this study, a median VPA cytotoxicity of 13.88% with a range of 0-54.65% was observed. Annexin V/PI staining confirmed that the demonstrated cytotoxicity was caused by increased apoptosis in the VPA treated cells as compared to control cells. Statistical analysis showed that VPA’s effect on CLL cells depends on lactate dehydrogenase serum levels, but is independent of all other prognostic markers.
Conclusion. The results of the present experiments found that VPA at a clinically applicable concentration significantly induces apoptosis independently of the disease stage and might be a valuable therapeutic agent for all CLL patients.

Key words

apoptosis, CLL, chronic lymphocytic leukemia, VPA, valproic acid.

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