PXD077084

PXD077084 is an original dataset announced via ProteomeXchange.

Title	RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis
Description	Acute myeloid leukemia (AML) is an aggressive hematological malignancy arising from hematopoietic stem and progenitor cells (HSPCs). Current treatments often fail to eradicate AML, therefore, new therapeutic strategies are essential. Here, we reveal that RNA Terminal-Uridylyl-Transferase-Enzymes 4 and 7 (TUT4/7) as novel druggable therapeutic targets, whose genetic deletion in AML suppresses growth, induces apoptosis and improves the survival of leukemic mice. Notably, a pre-clinical TUT4/7 inhibitor promotes cell death in AML patient samples and synergizes with Venetoclax. Mechanistically, TUT4/7 inactivation disrupts cellular metabolism and suppresses mevalonate pathway gene expression, compromising the prenylation and cholesterol synthesis pathways. Current AML therapies often cause severe hematopoietic toxicity. Although Tut4/7 deletion results in inflammatory activation throughout the hematopoietic system, this is permissive to a normal lifespan and Tut4/7-deficiency does not compromise HSPC function. Thus, we reveal TUT4/7 as druggable targets, whose inactivation suppresses AML while sparing normal hematopoiesis. In combination with Venetoclax this represents a novel and promising therapeutic strategy.
HostingRepository	PRIDE
AnnounceDate	2026-06-24
AnnouncementXML	Submission_2026-06-24_09:18:51.114.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-13 11:35:17	ID requested
⏵ 1	2026-06-24 09:18:51	announced

Dataset with its publication pending

submitter keyword: AML, Terminal Uridylyl-Transferases, HSPC

Jyoti Choudhary
contact affiliation	Functional Proteomics, ICR
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD077084
     1. Label: PRIDE project
     2. Name: RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis