PXD025231 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia |
Description | Genome-scale functional genetic screening was utilized to identify resistance mechanisms and synthetic lethal interactions during small molecule targeting of MENIN and DOT1L in MLL1-rearranged AML. Chromatin regulatory complexes are found to modulate the therapeutic response to these inhibitors, and IKZF1/IKAROS is identified as an essential transcriptional regulator that supports leukemia gene expression through extensive chromatin co-occupancy with MENIN and the transcription factor MEIS1. Furthermore, we show that combined IKAROS degradation with imide drugs and MENIN inhibition using VTP-50469 leads to synergistic anti-leukemic effects through rapid induction of apoptotic cell death both in vitro and in vivo. This study uncovers a previously underappreciated role for IKAROS in AML and cooperativity among IKAROS, MLL1/MENIN and MEIS1 in maintaining leukemogenic transcription. |
HostingRepository | PRIDE |
AnnounceDate | 2022-03-11 |
AnnouncementXML | Submission_2022-03-10_16:07:31.631.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Eric Fischer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-04-06 19:46:44 | ID requested | |
⏵ 1 | 2022-03-10 16:07:31 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: IKAROS, IKZF1, MENIN, MEN1, DOT1L, KMT2A, MLL1, acute myeloid leukemia, lenalidomide, IMiD |
Contact List
Eric Fischer |
contact affiliation | Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA |
contact email | Eric_Fischer@dfci.harvard.edu |
lab head | |
Eric Fischer |
contact affiliation | Dana-Farber Cancer Institute |
contact email | eric_fischer@dfci.harvard.edu |
dataset submitter | |
Full Dataset Link List
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://ftp.pride.ebi.ac.uk/pride/data/archive/2022/03/PXD025231 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD025231
- Label: PRIDE project
- Name: IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia