PXD025271-1

PXD025271 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_07:03:19.012.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	biotinylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-08 07:49:31	ID requested
⏵ 1	2022-05-31 07:03:19	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

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/PXD025271

PRIDE project URI

• PRIDE
  1. PXD025271
     1. Label: PRIDE project
     2. Name: IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia