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Open Access 01-12-2010 | SPECIAL ISSUE ARTICLE

The DAC system and associations with acute leukemias and myelodysplastic syndromes

Authors: Gesine Bug, Oliver G. Ottmann

Published in: Investigational New Drugs | Special Issue 1/2010

Summary

Imbalances of histone acetyltransferase (HAT) and deacetylase activity (DAC) that result in deregulated gene expression are commonly observed in leukemias. These alterations provide the basis for novel therapeutic approaches that target the epigenetic mechanisms implicated in leukemogenesis. As the acetylation status of histones has been linked to transcriptional regulation of genes involved particularly in differentiation and apoptosis, DAC inhibitors (DACi) have attracted considerable attention for treatment of hematologic malignancies. DACi encompass a structurally diverse family of compounds that are being explored as single agents as well as in combination with chemotherapeutic drugs, small molecule inhibitors of signaling pathways and hypomethylating agents. While DACi have shown clear evidence of activity in acute myeloid leukemia, myelodysplastic syndromes and lymphoid malignancies, their precise role in treatment of these different entities remain to be elucidated. Successful development of these compounds as elements of novel targeted treatment strategies for leukemia will require that clinical studies be performed in conjunction with translational research including efforts to identify predictive biomarkers.

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Title: The DAC system and associations with acute leukemias and myelodysplastic syndromes
Authors: Gesine Bug
Oliver G. Ottmann
Publication date: 01-12-2010
Publisher: Springer US
Published in: Investigational New Drugs / Issue Special Issue 1/2010
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-010-9595-z

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