Abstract
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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Abbreviations
- ALL:
-
Acute lymphoblastic leukemia
- AML:
-
Acute myeloid leukemia
- BCA:
-
Bicinchoninic acid assay
- BSA:
-
Bovine serum albumin
- CBP:
-
CREB-binding protein
- CLL:
-
Chronic lymphocytic leukemia
- FAB:
-
French-American-British Classification
- FDA:
-
Food and Drug Administration
- FLT3:
-
Fms-like tyrosine kinase 3
- GCN5:
-
General control of amino acid synthesis 5
- EDTA:
-
Ethylene-diamine-teraacetic acid
- ETO:
-
Eight twenty one
- HAT:
-
Histone acetyltransferase
- HDAC:
-
Histone deacetylase
- HCL:
-
Hairy cell leukemia
- HL:
-
Hodgkin lymphoma
- hMOF:
-
Human orthologue of the Drosophila melanogaster males absent on the first gene
- HMT:
-
Histone methyltransferase
- ITD:
-
Internal tandem duplication
- JAK:
-
Janus kinase
- MDS:
-
Myelodysplastic syndrome
- MLL:
-
Mixed lineage leukemia
- MPAL:
-
Mixed-phenotype acute leukemia
- NCOR:
-
Nuclear receptor co-repressor
- NPM1:
-
Nucleophosmin 1
- NuRD:
-
Nucleosome remodeling deacetylase
- PBX:
-
Pre-B-cell leukemia homeobox
- PCBP2:
-
Poly(C)-binding protein 2
- PRL3:
-
Phosphatase of regenerating liver cell 3
- qPCR:
-
Quantitative polymerase chain reaction
- RT:
-
Reverse transcription
- SAHA:
-
Suberoylannilide hydroxamic acid
- SDS:
-
Sodium dodecyl sulfate
- SIRT:
-
Sirtuin
- SMRT:
-
Silencing mediator of retinoid and thyroid hormone receptor
- STAT:
-
Signal transducers and activators of transcription
- TKD:
-
Tyrosine kinase domain
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Acknowledgments
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.
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Author Contributions
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
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DOI: https://doi.org/10.1007/s12253-016-0139-5