An immediate transcriptional signature associated with response to the histone deacetylase inhibitor Givinostat in T acute lymphoblastic leukemia xenografts View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-01-14

AUTHORS

M Pinazza, C Borga, V Agnusdei, S Minuzzo, G Fossati, M Paganin, B Michielotto, A De Paoli, G Basso, A Amadori, G te Kronnie, S Indraccolo

ABSTRACT

Despite some success with certain hematological malignancies and in contrast with the strong pro-apoptotic effects measured in vitro, the overall response rate of acute lymphoblastic leukemia (ALL) to histone deacetylase inhibitors (HDACis) is low. With the aim to improve the understanding of how HDACis work in vivo, we investigated the therapeutic efficacy of the clinically approved HDACi Givinostat in a collection of nine pediatric human T-ALL engrafted systemically in NOD/SCID mice. We observed highly heterogeneous antileukemia responses to Givinostat, associated with reduction of the percentage of infiltrating blasts in target organs, induction of apoptosis and differentiation. These effects were not associated with the T-ALL cytogenetic subgroup. Transcriptome analysis disclosed an immediate transcriptional signature enriched in genes involved in cell-cycle regulation and DNA repair, which was validated by quantitative RT-PCR and was associated with in vivo response to this HDACi. Increased phospho-H2AX levels, a marker of DNA damage, were measured in T-ALL cells from Givinostat responders. These results indicate that the induction of the DNA damage response could be an early biomarker of the therapeutic effects of Givinostat in T-ALL models. This information should be considered in the design of future clinical trials with HDACis in acute leukemia. More... »

PAGES

e2047

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cddis.2015.394

DOI

http://dx.doi.org/10.1038/cddis.2015.394

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1001567052

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26764573


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/cddis.2015.394'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/cddis.2015.394'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/cddis.2015.394'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/cddis.2015.394'


 

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300 schema:name Italfarmaco S.p.A, Milano, Italy
301 rdf:type schema:Organization
302 https://www.grid.ac/institutes/grid.5608.b schema:alternateName University of Padua
303 schema:name Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
304 Oncohematology Laboratory, Department of Woman and Child Health, University of Padova, Padova, Italy
305 rdf:type schema:Organization
 




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