PXD004442 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Phosphoproteome Analysis Reveals Differential Mode of Action of Sorafenib in Wildtype and Mutated FLT3 AML Cells |
Description | Constitutively activating internal tandem duplication (ITD) alterations of the receptor tyrosine kinase FLT3 (Fms-like tyrosine kinase 3) are common in acute myeloid leukemia (AML) and classifies FLT3 as an attractive therapeutic target. So far, application of FLT3 small molecule inhibitors such as Sorafenib has resulted only in partial and transient clinical responses in FLT3-ITD+ patients. Only recently, a prolonged event-free survival has been observed in AML patients who were treated with Sorafenib in addition to standard therapy. Here, we studied the Sorafenib effect on proliferation in a panel of 13 FLT3-ITD- and FLT3-ITD+ AML cell lines. Sorafenib IC50 values ranged from 0.001 to 5.6 µM, whereas FLT3-ITD+ cells (MOLM-13, MV4;11) were found more sensitive to Sorafenib than FLT3-ITD- cells. However, we identified two FLT3-ITD- cell lines (MONO-MAC-1 and OCI-AML-2) which were also Sorafenib sensitive. Phosphoproteome analyses revealed that the affected pathways differed in Sorafenib sensitive FLT3-ITD- and FLT3-ITD+ cells. In MV4;11 cells Sorafenib suppressed mTOR signalling by inhibiting direct inhibition of FLT3. In MONO-MAC-1 cells Sorafenib inhibited the MEK/ERK pathway by inhibition of the RET tyrosine kinase. These data suggest that the FLT3 status in AML patients might not be the only predictive factor for a response to Sorafenib. |
HostingRepository | PRIDE |
AnnounceDate | 2017-05-02 |
AnnouncementXML | Submission_2017-05-02_05:08:03.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Christoph Schaab |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2016-06-27 01:35:13 | ID requested | |
⏵ 1 | 2017-05-02 05:08:05 | announced | |
Publication List
Roolf C, Dybowski N, Sekora A, Mueller S, Knuebel G, Tebbe A, Murua Escobar H, Godl K, Junghanss C, Schaab C, Phosphoproteome Analysis Reveals Differential Mode of Action of Sorafenib in Wildtype and Mutated FLT3 Acute Myeloid Leukemia (AML) Cells. Mol Cell Proteomics, 16(7):1365-1376(2017) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Acute myeloid Leukemia, FLT3, Phosphoproteomics, Sorafenib |
Contact List
Christoph Schaab |
contact affiliation | Evotec (München) GmbH, Martinsried, Germany |
contact email | christoph.schaab@evotec.com |
lab head | |
Christoph Schaab |
contact affiliation | Evotec |
contact email | christoph.schaab@evotec.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD004442
- Label: PRIDE project
- Name: Phosphoproteome Analysis Reveals Differential Mode of Action of Sorafenib in Wildtype and Mutated FLT3 AML Cells