Histone deacetylase enzymes, confirmed to have important role in the pathogenesis of leukemia, are promising targets of epigenetic treatment. However, in acute myeloid leukemia, our knowledge on their expression levels is limited, and controversial data have been published about their potential oncogenic or tumorsuppressor properties in solid tumors. In our study, the expression levels of HDAC4 and SIRT6 were evaluated via Western blot analysis in 45 bone marrow samples (2 uninfiltrated and 43 concerned by different kinds of hematological malignancies), including 32 specimens obtained from patients with newly diagnosed AML. Significantly higher HDAC4 level was detected in case of FLT3-ITD mutation compared to the group of patients without carrying this mutation (p < 0.05). Compared to the non-infiltrated samples, the expression level of HDAC4 in AML M5 patients has been proved to be significantly higher (p < 0.05). Decreasing expression levels of both HDAC4 and SIRT6 were observed during the induction treatment of FAB M5 type AML. Strong correlation has been proved between the expression levels of HDAC4 and SIRT6 (r = 0.722 in full cohort and r = 0.794 in AML), that confirms the recently suggested cooperation between NAD+-independent and NAD+-dependent HDAC enzymes in leukemia.
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Acute lymphoblastic leukemia
Acute myeloid leukemia
Bicinchoninic acid assay
Bovine serum albumin
Chronic lymphocytic leukemia
Food and Drug Administration
Fms-like tyrosine kinase 3
General control of amino acid synthesis 5
Eight twenty one
Hairy cell leukemia
Human orthologue of the Drosophila melanogaster males absent on the first gene
Internal tandem duplication
Mixed lineage leukemia
Mixed-phenotype acute leukemia
Nuclear receptor co-repressor
Nucleosome remodeling deacetylase
Pre-B-cell leukemia homeobox
Poly(C)-binding protein 2
Phosphatase of regenerating liver cell 3
Quantitative polymerase chain reaction
Suberoylannilide hydroxamic acid
Sodium dodecyl sulfate
Silencing mediator of retinoid and thyroid hormone receptor
Signal transducers and activators of transcription
Tyrosine kinase domain
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The authors are grateful for Dóra Dedinszki, Zoltán Kónya (Department of Medical Chemistry, University of Debrecen) and Zsuzsanna Nagy (Department of Physiology, University of Debrecen) for the useful technical advices.
Our work was partially financed by Astellas Pharma Ltd.
Conflict of Interest
The authors declare that they have no conflict of interest.
Gaál Zs.: experimental procedures, design research, data analysis, writing the manuscript.
Oláh É.: design research, supervision of experimental procedures, correction of the manuscript.
Rejtő L.: collection of bone marrow specimens.
Erdődi F.: providing laboratory background (Department of Medical Chemistry), design research, supervision of experimental procedures, correction of the manuscript.
Csernoch L.: design research, supervision of experimental procedures, correction of the manuscript.
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Gaál, Z., Oláh, É., Rejtő, L. et al. Strong Correlation between the Expression Levels of HDAC4 and SIRT6 in Hematological Malignancies of the Adults. Pathol. Oncol. Res. 23, 493–504 (2017). https://doi.org/10.1007/s12253-016-0139-5
- Acute myeloid leukemia
- Histone deacetylation