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Title: The HDAC inhibitor panobinostat (LBH589) inhibits Acute Lymphoblastic leukemia (ALL) in vitro and in vivo in a new characterized human ALL mice model (ALL-B and ALL-T)      
dateReleased:
04-17-2012
description:
Histone deacetylases (HDACs) have been identified as therapeutic targets due to regulatory function in DNA structure and organization. We have analyzed the role of the LBH589, a novel pan inhibitor of class I and II HDACs, in Acute Lymphoblastic Leukemia. In vitro, LBH589 was shown to induce a dose dependent antiproliferative and apoptotic effect which was associated with an increase in the acetylation of H3 and H4 histone acetylation which was uniformly in every genetic subgroup of ALL. In vivo administration of LBH589 in BALB/c-RAG2-/-γc-/- mice in which T and B-cell leukemic cell lines were injected induced a significant reduction in tumor growth (TOM-1, p<0.01 and MOLT-4 p<0.05). Leukemic cells from patients were employed to establish a xenograft model of human leukemia in BALB/c-RAG2-/-γc-/- mice and further transplanted in consecutive generations of mice. Treatment of these xenografts with LBH589 induced an increase in the acetylation of H3 and H4 and prolonged the survival of mice in comparison with the animals treated with Vincristine and Dexametasone (p<0.05) and this effect was significantly higher when LBH589 was combined with Vincristine and Dexametasone (p<0.001). Our results that the use of LBH589 in combination with standard chemotherapy represents an attractive option for treatment of patients with ALL. Two primary samples of ALL (one ALL-B and one ALL-T) and two samples of each leukemia after passages in immunodeficient mice.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-26789
refinement:
raw
alternateIdentifiers:
26789
keywords:
functional genomics
dateModified:
09-16-2015
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-AFFY-141
name:
Affymetrix GeneChip Human Gene 1.0 ST Array [HuGene-1_0-st-v1]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-26789/E-GEOD-26789.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-26789/E-GEOD-26789.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26789
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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