PXD069587-1

PXD069587 is an original dataset announced via ProteomeXchange.

Title	Canagliflozin synergises with serine synthesis pathway inhibition mediating anti-leukaemic effects in T-cell acute lymphoblastic leukaemia
Description	T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy commonly driven by NOTCH1 activating mutations. A concomitant feature associated with NOTCH1 mutations is heightened oxidative metabolism enabling the exponential proliferation of T-ALL blasts. As such, targeting mitochondrial metabolism in T-ALL is an attractive therapeutic avenue. Canagliflozin (cana) is an FDA-approved sodium glucose co-transporter 2 inhibitor with known off-target effects on complex I and glutamate dehydrogenase. To date, the effects of cana on T-ALL are not known. Here, we show that cana possesses potent anti-leukaemic effects underpinned by proliferative defects, cell cycle disruption and apoptosis. These anti-leukaemic effects, driven by cana, are attributed to a perturbed tricarboxylic acid (TCA) cycle and mitochondrial metabolism and elevated mitochondrial ROS. Proteomic analysis revealed that cana treatment resulted in a compensatory increase in the expression of ATF4 targets, including upregulation of serine biosynthesis pathway and one-carbon metabolism enzymes. As such, restriction of serine and glycine synergized with cana treatment, further enhancing anti-leukaemic effects. Collectively, our study reveals cana creates a metabolic vulnerability that can be further exploited via dietary manipulation to treat T-ALL
HostingRepository	PRIDE
AnnounceDate	2025-10-27
AnnouncementXML	Submission_2025-10-27_03:48:53.312.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fernando Manuel Garcia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-17 05:23:45	ID requested
⏵ 1	2025-10-27 03:48:53	announced

10.1016/J.MOLMET.2025.102275;

submitter keyword: LC-MSMS,T-ALL, cell line

Nick Jones
contact affiliation	Faculty of Medicine Health and Life Science Medical School Swansea University Wales
contact email	N.Jones@Swansea.ac.uk
lab head
Fernando Manuel Garcia
contact affiliation	Swansea University
contact email	f.m.poncegarcia@swansea.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069587
     1. Label: PRIDE project
     2. Name: Canagliflozin synergises with serine synthesis pathway inhibition mediating anti-leukaemic effects in T-cell acute lymphoblastic leukaemia