⮝ Full datasets listing
PXD069508
PXD069508 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | NRAS knockdown reverses monocytic cell state and resensitizes resistant FLT3-AML cells to gilteritinib |
| Description | Gilteritinib is initially effective in acute myeloid leukemia (AML) patients with FLT3 mutations, however they invariably relapse after only months of treatment. Resistance is commonly associated with emergence of NRAS mutations and more monocytic cell state. We hypothesized that directly targeting NRAS would restore sensitivity to FLT3i. We utilized a mutation-agnostic antisense oligonucleotide (ASO) to selectively knockdown NRAS expression in gilteritinib-resistant AML cell lines and primary patient samples with NRAS mutations, effectively restoring sensitivity to gilteritinib. Efficacy of NRAS ASO was independent of NRAS variant allele frequency in primary AML samples and superior to downstream MEK inhibition. Multi-omic analyses (transcriptomics, proteomics, phosphoproteomics) revealed that NRAS knockdown reversed the monocytic phenotype, conferring a more primitive cell state. Monocytic cell state and NRAS mutations are known to drive resistance to venetoclax and other targeted therapies in AML, suggesting that reversing monocytic cell state with NRAS ASO may have applications beyond gilteritinib resistance. Data was searched with MS-GF+ using PNNL's DMS Processing pipeline. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-06-24 |
| AnnouncementXML | Submission_2026-06-24_20:01:37.008.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Matthew Monroe |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Carbamidomethyl; Phospho; TMTpro |
| Instrument | Orbitrap Ascend; Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-10-15 21:06:47 | ID requested | |
| ⏵ 1 | 2026-06-24 20:01:37 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: AML, NRAS, gilteritinib, drug resistance, phosphoproteomics, DatasetType:Proteomics |
Contact List
| Paul D. Piehowski | |
|---|---|
| contact affiliation | Pacific Northwest National Laboratory |
| contact email | paul.piehowski@pnnl.gov |
| lab head | |
| Matthew Monroe | |
| contact affiliation | Pacific Northwest National Laboratory |
| contact email | matthew.monroe@pnnl.gov |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v11/MSV000099508/ |
