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| Status |
Public on May 06, 2021 |
| Title |
Pharmacological inhibition of WIP1 sensitizes acute myeloid leukemia cells to MDM2 inhibitor Nutlin-3a |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The wild-type p53-inducible protein phosphatase WIP1, encoded by the PPM1D gene, is a negative regulator of p53 and is involved in cell cycle control and DNA damage stress-response. In acute myeloid leukemia (AML), the restoration of p53 activity through MDM2 inhibition proved efficacy in a number of combination strategies. We investigated the therapeutic potential of its inhibition through the selective WIP1 inhibitor (WIP1i) GSK2830371, in association with the MDM2 inhibitor Nutlin-3a (Nut-3a) in a panel of AML cell lines and performed gene expression analysis of single agent and combined treatments. A p53-related signature was significantly upregulated in the TP53-wildtype MV-4-11 AML cell line. Moreover, drug-specific transcriptional changes likely contribute to the synergistic combination effect.
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| Overall design |
TP53-wildtype MV-4-11 and TP53-mutated NOMO-1 cells treated with Nutlin-3a or GSK2830371, or the drug combination (or vehicle) for 16h were used for RNA extraction and hybridization on microarrays.
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| Contributor(s) |
Simonetti G, Fontana MC, Pazzaglia M, Martinelli G |
| Citation(s) |
33917342 |
| Submission date |
Aug 13, 2020 |
| Last update date |
May 06, 2021 |
| Contact name |
Giorgia Simonetti |
| E-mail(s) |
giorgia.simonetti@irst.emr.it
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| Organization name |
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
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| Lab |
Giorgia Simonetti
|
| Street address |
Via Piero Maroncelli, 40
|
| City |
Meldola |
| State/province |
FC |
| ZIP/Postal code |
47014 |
| Country |
Italy |
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| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA657008 |
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