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| Status |
Public on Dec 31, 2014 |
| Title |
Inhibitor of apoptosis protein antagonist BV6 – potential for new combinatorial treatment strategies in acute myeloid leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Apoptosis is deregulated in most, if not all, cancers, including hematological malignancies. In this study, we wanted to test whether primary acute myeloid leukemia (AML) samples are sensitive for inhibitor of apoptosis (IAP) protein antagonist treatment in vitro, and which AML subgroup might profit most from such a novel therapeutic strategy. We treated diagnostic samples of 67 adult AML patients with either cytarabine (ara-C) or IAP antagonist BV6 and correlated sensitivity with clinical, cytogenetic and molecular markers, and expression levels of selected genes involved in apoptosis. Primary AML samples showed differential sensitivity to treatment with either ara-C (40% sensitive, 17% intermediate, 43% resistant) or BV6 (51% sensitive, 21% intermediate, 28% resistant). Notably, 69% of ara-C resistant samples showed a good to fair response to IAP inhibition. Furthermore, combination treatment of ara-C with BV6 showed additive effects in most samples. Differences in sensitivity to IAP antagonist treatment correlated with significantly elevated expression levels of TNF and lower levels of XIAP in BV6 sensitive samples, as well as with NPM1 mutations. Gene expression profiling pointed to apoptosis-related pathways, which were specifically induced by IAP inhibition in sensitive samples. Thus, our results suggest IAP inhibition as a potential novel therapeutic option in AML.
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| Overall design |
Gene expression was profiled in 24 AML samples [n=12 untreated, diagnostic samples of BV6 resistant (n=6) and sensitive (n=6) cases; n=6 paired samples (BV6 sensitive n=3 and resistant n=3 cases) treated for 24 hours with either DMSO or BV6].
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| Contributor(s) |
Lück SC, Bullinger L |
| Citation(s) |
26096065, 27385100 |
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| Submission date |
May 10, 2013 |
| Last update date |
Sep 27, 2019 |
| Contact name |
Lars Bullinger |
| E-mail(s) |
lars.bullinger@charite.de
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| Phone |
+49-30-450-553111
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| Organization name |
Charité
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| Department |
Hematology, Oncology and Tumorimmunology
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| Street address |
Augustenburger Platz 1
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| City |
Berlin |
| ZIP/Postal code |
13353 |
| Country |
Germany |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA202397 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46819_RAW.tar |
103.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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