Journal article
Compounds targeting class II histone deacetylases do not cause panHDACI-associated impairment of megakaryocyte differentiation
Experimental hematology, v 72
01 Apr 2019
PMID: 30611870
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Histone deacetylase inhibitors (HDACIs) have demonstrated effectiveness against lymphomas and myelomas in clinical practice. However, common to all currently approved broad-acting HDACIs (panHDACIs) is dose-limiting thrombocytopenia, which has prevented wider use in cancer therapy. Using CD34(+) hematopoietic stem cells (HSCs), we show that megakaryocyte (MK) cell maturation and differentiation are impaired by panHDACIs, correlating to clinical thrombocytopenia. Importantly, we demonstrate that inhibitors of class II histone deacetylases (HDACs), including LMK235 and tubacin at clinically relevant concentrations, do not affect MK maturation. Furthermore, we show that HDACI-induced impairment of MK differentiation is associated with reduction of protein levels of the transcription factor GATA-1, but not tubulin hyper-acetylation. Finally, we report that panHDACIs trigger a rapid loss of GATA-1 protein via a proteasome-dependent pathway. Our data support the notion that specifically targeting class II HDACs in cancer treatment is a potential strategy that would offer a safer alternative than current panHDACIs. (C) 2019 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
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Details
- Title
- Compounds targeting class II histone deacetylases do not cause panHDACI-associated impairment of megakaryocyte differentiation
- Creators
- Damir Simic - Drexel UniversityNianli Sang - Drexel University
- Publication Details
- Experimental hematology, v 72
- Publisher
- Elsevier
- Number of pages
- 11
- Grant note
- Lipogen State of Pennsylvania (CURE grant) ROl-CA129494 / National Cancer Institute of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000464090000005
- Scopus ID
- 2-s2.0-85059665383
- Other Identifier
- 991019167907004721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Hematology
- Medicine, Research & Experimental