|
| Status |
Public on Apr 18, 2012 |
| 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) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
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| 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.
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| Contributor(s) |
Vilas-Zornoza A, Agirre X, Abizanda G, Moreno C, Segura V, Rodriguez AD, San José-Eneriz E, Blanco-Prieto5 M, García de Jalón JA, Rifón J, Cigudosa JC, Martinez-Climent JA, Román-Gómez J, Calasanz MJ, Prósper F |
| Citation(s) |
22307227 |
| Submission date |
Jan 21, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Xabier Agirre |
| E-mail(s) |
xaguirre@unav.es
|
| Phone |
+34 948194700
|
| Organization name |
CIMA
|
| Department |
Oncology
|
| Street address |
Pio XII, 55
|
| City |
Pamplona |
| State/province |
Navarra |
| ZIP/Postal code |
31008 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (6)
|
| GSM659126 |
Primary sample of B cell Acute Lymphoblastic Leukemia |
| GSM659127 |
B cell Acute Lymphoblastic Leukemia 421 |
| GSM659128 |
B cell Acute Lymphoblastic Leukemia 739 |
| GSM659129 |
Primary sample of T cell Acute Lymphoblastic Leukemia |
| GSM659130 |
T cell Acute Lymphoblastic Leukemia 1 |
| GSM659131 |
T cell Acute Lymphoblastic Leukemia 226 |
|
| This SubSeries is part of SuperSeries: |
| GSE26807 |
The HDAC inhibitor panobinostat (LBH589) inhibits Acute Lymphoblastic leukemia (ALL) in vitro and in vivo in a new characterized human ALL mice model |
|
| Relations |
| BioProject |
PRJNA142113 |
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