Fol. Biol. 2010, 56, 201-205

https://doi.org/10.14712/fb2010056050201

The Effect of a Histone Deacetylase Inhibitor – Valproic Acid – on Nucleoli in Human Leukaemic Myeloblasts

Karel Smetana1, M. Zápotocký2

1Institute of Haematology and Blood Transfusion, Prague, Czech Republic
2Charles University in Prague, 2nd Faculty of Medicine, Prague, Czech Republic

Received May 2010
Accepted June 2010

The present study was undertaken to provide more information on nucleolar changes induced by a histone deacetylase inhibitor such as valproic acid in leukaemic myeloblasts at the single-cell level. For this study, RNA in nucleoli was visualized by a simple but sensitive cytochemical procedure in unfixed cytospins of short-term bone marrow cultures from patients suffering from acute myeloid leukaemia. Valproic acid in leukaemic myeloblasts markedly reduced the nucleolar size and also produced significant transformation of “active” to “resting” and “inactive” nucleoli that reflected the alteration of the nucleolar transcription in sensitive myeloblasts. On this occasion it should be added that valproic acid significantly increased the incidence of altered myeloblasts that changed to apoptotic cells or apoptotic bodies and cell ghosts. In contrast to the above-mentioned decreased nucleolar size, the nucleolar RNA concentration, expressed by computerassisted RNA image densitometry in valproic acidtreated myeloblasts, was not significantly changed. The results of the present study clearly indicated that the nucleolar size and transformation of “active” to “sleeping” or “inactive” nucleoli are convenient markers of the sensitivity and alteration of leukaemic myeloblasts produced by a histone deacetylase inhibitor, valproic acid, at the single-cell level.

Funding

The present study was supported in part by the Research Development Project VZ 0002373601 of the Ministry of Health of the Czech Republic and Research Development Project VZ 0021620813 of the Ministry of Education, Youth and Sports of the Czech Republic.

References

28 live references