期刊
CELLS
卷 10, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/cells10051088
关键词
chronic lymphocytic leukemia; chlorambucil and valproic acid; apoptosis; T53 and Bcl-2 family genes; cytogenetic prognostics
类别
The combination of chlorambucil and valproic acid may lead to increased apoptosis in CLL cells and elevated expression of important genes, suggesting further investigation into this treatment approach for CLL.
Malignant cells in chronic lymphocytic leukemia (CLL) show resistance to apoptosis, as well as to chemotherapy, which are related to deletions or mutations of TP53, high expression of MCL1 and BCL2 genes and other abnormalities. Thus, the main goal of the present study was to assess the impact of chlorambucil (CLB) combined with valproic acid (VPA), a known antiepileptic drug and histone deacetylation inhibitor, on apoptosis of the cells isolated from 17 patients with CLL. After incubation with CLB (17.5 mu M) and VPA (0.5 mM), percentage of apoptosis, as well as expression of two TP53 target genes (p21 and HDM2) and two genes from Bcl-2 family (BCL2 and MCL1), were tested. As a result, an increased percentage of apoptosis was observed for CLL cells treated with CLB and VPA, and with CLB alone. Under the treatment with the drug combination, the expression of p21 gene was visibly higher than under the treatment with CLB alone. At the same time, the cultures under CLB treatment showed visibly higher expression of BCL2 than the cultures with VPA alone. Thus, the present study strongly suggests further investigations on the CLB and VPA combination in CLL treatment.
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