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PXD025271-1

PXD025271 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia
DescriptionGenome-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.
HostingRepositoryPRIDE
AnnounceDate2022-05-31
AnnouncementXMLSubmission_2022-05-31_07:03:19.012.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEric Fischer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListbiotinylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-08 07:49:31ID requested
12022-05-31 07:03:19announced
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 affiliationDepartment 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 emaileric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliationDana-Farber Cancer Institute
contact emaileric_fischer@dfci.harvard.edu
dataset submitter
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Dataset FTP location
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