PXD066495-1

PXD066495 is an original dataset announced via ProteomeXchange.

Title	Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia
Description	The ubiquitous metabolite heme has diverse enzymatic and signaling functions in most mammalian cells. Through integrated analyses of mouse models, human cell lines and primary patient samples, we identify de novo heme biosynthesis as a selective dependency in acute myeloid leukemia (AML). The dependency is underpinned by a propensity of AML cells, and especially leukemic stem cells (LSCs), to downregulate heme biosynthesis enzymes (HBEs) which promotes their self-renewal. Inhibition of HBEs causes collapse of mitochondrial Complex IV (CIV) and dysregulates the copper-chaperone system inducing cuproptosis, a form of programmed cell death brought about by the oligomerization of lipoylated proteins by copper. Moreover, we identify pathways that are synthetic lethal with heme biosynthesis, including glycolysis, which can be leveraged for combination strategies. Altogether, our work uncovers a heme rheostat that controls gene expression and drug sensitivity in AML and implicates HBE inhibition as a novel cuproptosis trigger.
HostingRepository	PRIDE
AnnounceDate	2025-11-12
AnnouncementXML	Submission_2025-11-11_21:35:12.782.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ching-Seng Ang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-23 18:34:04	ID requested
⏵ 1	2025-11-11 21:35:13	announced

10.1016/J.CELL.2025.10.028;

submitter keyword: AML heme copper

Lev Kats
contact affiliation	Peter MacCallum Cancer Centre, Melbourne, 3000, Victoria, Australia
contact email	Lev.kats@petermac.org
lab head
Ching-Seng Ang
contact affiliation	University of Melbourne
contact email	cang@unimelb.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066495
     1. Label: PRIDE project
     2. Name: Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia