PXD014387-1

PXD014387 is an original dataset announced via ProteomeXchange.

Title	FBXO9 in Murine Inversion 16 AML
Description	The hematopoietic system is maintained throughout life by hematopoietic stem cells that are capable of differentiation to all hematopoietic lineages. An intimate balance between self-renewal, differentiation, and quiescence is required to maintain hematopoiesis. Disruption of this balance can result in hematopoietic malignancy, including acute myeloid leukemia (AML). FBXO9, from the F-box ubiquitin E3 ligases, is down-regulated in patients with AML compared to normal bone marrow. FBXO9 is a substrate recognition component of the Skp1-Cullin-F-box (SCF)-type E3 ligase complex. FBXO9 is highly expressed in hematopoietic stem and progenitor populations, which contain the tumor-initiating population in AML. In AML patients, decrease in FBXO9 expression is most pronounced in patients with the inversion of chromosome 16 (Inv(16)), a rearrangement that generates the transcription factor fusion gene, CBFB-MYH11. To study FBXO9 in malignant hematopoiesis, we generated a conditional knockout mouse model using a novel CRISPR/Cas9 strategy. Our data shows that deletion of Fbxo9 in mice expressing Cbfb-MYH11 leads to markedly accelerated and aggressive leukemia development. In addition, we find loss of FBXO9 leads to increased proteasome expression and tumors are more sensitive to bortezomib suggesting that FBXO9 expression may predict patient response to bortezomib treatment.
HostingRepository	PRIDE
AnnounceDate	2019-11-27
AnnouncementXML	Submission_2019-11-27_02:02:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Samantha Swenson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; ubiquitination signature dipeptidyl lysine; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-26 01:30:10	ID requested
⏵ 1	2019-11-27 02:02:16	announced
2	2024-10-22 04:11:50	announced	2024-10-22: Updated project metadata.

Hynes-Smith RW, Swenson SA, Vahle H, Wittorf KJ, Caplan M, Amador C, Hyde RK, Buckley SM, Loss of FBXO9 Enhances Proteasome Activity and Promotes Aggressiveness in Acute Myeloid Leukemia. Cancers (Basel), 11(11):(2019) [pubmed]

submitter keyword: FBXO9 AML Inv(16) Spleen

Shannon Mychel Buckley
contact affiliation	Department of Genetics, Cell Biology, & Anatomy Buckley Lab University of Nebraska Medical Center Omaha, Nebraska United States of America
contact email	shannon.buckley@unmc.edu
lab head
Samantha Swenson
contact affiliation	University of Nebraska Medical Center
contact email	samantha.swenson@unmc.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/2019/11/PXD014387

PRIDE project URI

• PRIDE
  1. PXD014387
     1. Label: PRIDE project
     2. Name: FBXO9 in Murine Inversion 16 AML