PXD028481-1

PXD028481 is an original dataset announced via ProteomeXchange.

Title	ZNF384 fusion oncoproteins drive lineage aberrancy in acute leukemia
Description	ZNF384-rearranged fusion oncoproteins (FO) define a subset of lineage ambiguous leukemias, but the mechanistic role of ZNF384 FO in leukemogenesis and lineage ambiguity is poorly understood. Here, using viral expression in mouse and human hematopoietic stem and progenitor cells (HSPCs) and a Ep300-Zfp384 mouse model we show that ZNF384 FO promote hematopoietic expansion, myeloid lineage skewing, and self-renewal. In mouse HSPCs, concomitant lesions such as NRASG12D, were required for fully penetrant leukemia, whereas expression of ZNF384 FO drove development of B/myeloid leukemia in human HSPCs, with sensitivity of human ZNF384r leukemia to FLT3 inhibition in vivo. Mechanistically, ZNF384 FO occupy a subset of predominantly intragenic/enhancer regions with increased histone 3 lysine acetylation suggesting enhancer function. These data define a paradigm for FO-driven lineage ambiguous leukemia, in which expression in HSPCs results in deregulation of lineage-specific genes and hematopoietic skewing, progressing to full leukemic transformation in the presence of proliferative stress.
HostingRepository	PRIDE
AnnounceDate	2022-03-16
AnnouncementXML	Submission_2022-03-16_09:39:01.065.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evangelia Papachristou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-15 09:05:19	ID requested
⏵ 1	2022-03-16 09:39:01	announced

Dataset with its publication pending

submitter keyword: ZNF384, fusion oncoprotein, stem cell, lineage ambiguous, mixed phenotype, leukemia

Charles Mullighan
contact affiliation	Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, 38105 USA
contact email	Charles.Mullighan@STJUDE.ORG
lab head
Evangelia Papachristou
contact affiliation	Senior Scientific Assistant
contact email	Eva.Papachristou@cruk.cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028481
     1. Label: PRIDE project
     2. Name: ZNF384 fusion oncoproteins drive lineage aberrancy in acute leukemia