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Accession: PRJNA142119 ID: 142119

The HDAC inhibitor panobinostat (LBH589) inhibits Acute Lymphoblastic leukemia (ALL) in vitro and in vivo in a new characterized human ALL mice model (SNP) (human)

See Genome Information for Homo sapiens
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. Overall design: Two primary samples of ALL (one ALL-B and one ALL-T) and two samples of each leukemia after passages in immunodeficient mice.
AccessionPRJNA142119; GEO: GSE26792
ScopeMultiisolate
OrganismHomo sapiens[Taxonomy ID: 9606]
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo; Homo sapiens
PublicationsVilas-Zornoza A et al., "Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.", Leukemia, 2012 Feb 6;26(7):1517-26
SubmissionRegistration date: 18-Apr-2012
Oncology, CIMA
RelevanceMedical
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PubMed1
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GEO DataSets1
GEO Data Details
ParameterValue
Data volume, Spots1429824
Data volume, Processed Mbytes47
Data volume, Supplementary Mbytes143

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