PXD060758

PXD060758 is an original dataset announced via ProteomeXchange.

Title	Systematic silencing of oncogenic fusion transcripts with ultra-precise CRISPR-Cas13b
Description	Oncogenic gene fusions are key drivers of cancer, yet most remain untargetable by current therapies. Here, we establish CRISPR-PspCas13b as a personalizable platform for systematic silencing of various fusion transcripts. We reveal that recognition and cleavage of the breakpoint sequence by PspCas13b disrupts the fusion transcript, resulting in unexpected RNA nicking and ligation near the cleavage site, which generates out-of-frame, translation-incompetent transcripts. This approach efficiently degrades canonical and drug-resistant BCR::ABL1 mutants (e.g., T315I), a primary cause of resistance to tyrosine kinase inhibitors (TKIs) and relapse in chronic myeloid leukemia (CML). Silencing T315I BCR::ABL1 mRNA in drug-resistant CML cells triggers extensive transcriptomic, proteomic, and phosphoproteomic remodelling, causing erythroid differentiation and apoptosis. Beyond BCR-ABL1 mutants, personalized design of PspCas13b effectively silences other undruggable fusions, including RUNX1::RUNX1T1 and EWSR1::FLI1, key drivers in acute myeloid leukemia and Ewing sarcoma, respectively. Collectively, this study establishes a framework for systematic, precise, and personalizable targeting of otherwise undruggable or drug-resistant oncogenic transcripts.
HostingRepository	PRIDE
AnnounceDate	2026-09-01
AnnouncementXML	Submission_2026-09-01_06:28:42.670.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenxin Hu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-12 23:39:45	ID requested
⏵ 1	2026-09-01 06:28:43	announced

Dataset with its publication pending

submitter keyword: None

Mohamed Fareh
contact affiliation	Peter MacCallum Cancer Centre
contact email	mohamed.fareh@petermac.org
lab head
Wenxin Hu
contact affiliation	1Peter MacCallum Cancer Centre, Melbourne, 3000, Australia 2Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3052, Australia
contact email	wenxin.hu@petermac.org
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/2026/08/PXD060758

PRIDE project URI

• PRIDE
  1. PXD060758
     1. Label: PRIDE project
     2. Name: Systematic silencing of oncogenic fusion transcripts with ultra-precise CRISPR-Cas13b