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HDAC8 overexpression in mesenchymal stromal cells from JAK2 + myeloproliferative neoplasms: a new therapeutic target?

Overview of attention for article published in Oncotarget, March 2017
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Title
HDAC8 overexpression in mesenchymal stromal cells from JAK2 + myeloproliferative neoplasms: a new therapeutic target?
Published in
Oncotarget, March 2017
DOI 10.18632/oncotarget.15969
Pubmed ID
Authors

Teresa L. Ramos, Luis Ignacio Sánchez-Abarca, Alba Redondo, Ángel Hernández-Hernández, Antonio M. Almeida, Noemí Puig, Concepción Rodríguez, Rebeca Ortega, Silvia Preciado, Ana Rico, Sandra Muntión, José Ramón González Porras, Consuelo Del Cañizo, Fermín Sánchez-Guijo

Abstract

Histone deacetylases (HDACs) are involved in epigenetic modulation and their aberrant expression has been demonstrated in myeloproliferative neoplasms (MPN). HDAC8 inhibition has been shown to inhibit JAK2/STAT5 signaling in hematopoietic cells from MPN. Nevertheless, the role of HDAC8 expression in bone marrow-mesenchymal stromal cells (BM-MSC) has not been assessed. In the current work we describe that HDAC8 is significantly over-expressed in MSC from in JAK-2 positive MPN compared to those from healthy-donors (HD-MSC). Using a selective HDAC8 inhibitor (PCI34051), we verified that the subsequent decrease in the protein and mRNA expression of HDAC8 is linked with an increased apoptosis of malignant MSC whereas it has no effects on normal MSC. In addition, HDAC8 inhibition in MPN-MSC also decreased their capacity to maintain neoplastic hematopoiesis, by increasing the apoptosis, cell-cycle arrest and colony formation of JAK2+-hematopoietic cells. Mechanistic studies using different MPN cell lines revealed that PCI34051 induced their apoptosis, which is enhanced when were co-cultured with JAK2V617F-MSC, decreased their colony formation and the phosphorylation of STAT3 and STAT5. In summary, we show for the first time that the inhibition of HDAC8 in MSC from JAK2+ MPN patients selectively decreases their hematopoietic-supporting ability, suggesting that HDAC8 may be a potential therapeutic target in this setting by acting not only on hematopoietic cells but also on the malignant microenvironment.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 16%
Student > Master 3 16%
Other 2 11%
Student > Ph. D. Student 2 11%
Student > Doctoral Student 1 5%
Other 0 0%
Unknown 8 42%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 16%
Medicine and Dentistry 3 16%
Agricultural and Biological Sciences 1 5%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Neuroscience 1 5%
Other 1 5%
Unknown 9 47%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 April 2017.
All research outputs
#18,541,268
of 22,963,381 outputs
Outputs from Oncotarget
#8,464
of 14,336 outputs
Outputs of similar age
#235,110
of 307,980 outputs
Outputs of similar age from Oncotarget
#775
of 1,420 outputs
Altmetric has tracked 22,963,381 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 14,336 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 307,980 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1,420 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.