PXD028925

PXD028925 is an original dataset announced via ProteomeXchange.

Title	SFPQ-ABL1 and BCR-ABL1 utilise different signalling networks to drive B-cell acute lymphoblastic leukaemia
Description	Philadelphia-like (Ph-like) acute lymphoblastic leukaemia (ALL) is a high-risk subtype of B-cell ALL characterised by a gene expression profile resembling Philadelphia Chromosome positive ALL (Ph+ ALL) in the absence of BCR-ABL1. Tyrosine kinase activating fusions, some involving ABL1, are recurrent drivers of Ph-like ALL and are targetable with tyrosine kinase inhibitors (TKIs). We identified a rare instance of SFPQ-ABL1 in a child with Ph-like ALL. SFPQ-ABL1 expressed in cytokine-dependent cell lines was sufficient to transform cells which were sensitive to ABL1-targeting TKIs. In contrast to BCR-ABL1, SFPQ-ABL1 localised to the nuclear compartment and was a weaker driver of cellular proliferation. Phosphoproteomics analysis showed upregulation of cell cycle, DNA replication and spliceosome pathways, and downregulation of signal transduction pathways, including ErbB, NF-kappa B, VEGF, and MAPK signalling in SFPQ-ABL1-, compared to BCR-ABL1-expressing cells. SFPQ-ABL1 expression did not activate PI3K/AKT signalling and was associated with phosphorylation of G2/M cell cycle proteins. SFPQ-ABL1 was sensitive to navitoclax and S-63845 and promotes cell survival through upregulation of Mcl-1 and Bcl-xL. SFPQ-ABL1 has functionally distinct mechanisms by which it drives ALL, including subcellular localisation, proliferative capacity, and activation of cellular pathways, highlighting the role that fusion partners have in mediating the function of ABL1 fusions.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-19_22:05:15.896.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jarrod Sandow
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-04 10:01:45	ID requested
⏵ 1	2022-05-19 22:05:16	announced

Brown LM, Hediyeh-Zadeh S, Sadras T, Huckstep H, Sandow JJ, Bartolo RC, Kosasih HJ, Davidson NM, Schmidt B, Bjelosevic S, Johnstone R, Webb AI, Khaw SL, Oshlack A, Davis MJ, Ekert PG, SFPQ-ABL1 and BCR-ABL1 use different signaling networks to drive B-cell acute lymphoblastic leukemia. Blood Adv, 6(7):2373-2387(2022) [pubmed]

submitter keyword: Leukaemia, AML, SFPQ, BCR, ABL1

Paul Ekert
contact affiliation	Laboratory Head Children's Cancer Institute Lowy Cancer Research Centre, UNSW Australia PO Box 81 Randwick 2031 Australia
contact email	pekert@ccia.org.au
lab head
Jarrod Sandow
contact affiliation	WEHI
contact email	sandow@wehi.edu.au
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/2022/05/PXD028925

PRIDE project URI

• PRIDE
  1. PXD028925
     1. Label: PRIDE project
     2. Name: SFPQ-ABL1 and BCR-ABL1 utilise different signalling networks to drive B-cell acute lymphoblastic leukaemia