PXD025232

PXD025232 is an original dataset announced via ProteomeXchange.

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	2022-05-31
AnnouncementXML	Submission_2022-05-31_07:04:20.213.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

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-06 19:47:06	ID requested
⏵ 1	2022-05-31 07:04:20	announced

Dataset with its publication pending

submitter keyword: IKAROS, IKZF1, MENIN, MEN1, DOT1L, KMT2A, MLL1, acute myeloid leukemia, lenalidomide, IMiD

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

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PRIDE project URI

• PRIDE
  1. PXD025232
     1. Label: PRIDE project
     2. Name: IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia