PXD002004

PXD002004 is an original dataset announced via ProteomeXchange.

Title	Quantitative Proteomic Profiles of Chronic Lymphocytic Leukaemia
Description	Chronic lymphocytic leukaemia (CLL) is a common, adult B-cell leukaemia that has challenges in prognosis and treatment. It is characterised by a heterogeneous clinical course with multiple distinct phenotypes currently defined genetically or with target-specific monoclonal antibodies. While many studies have examined specific protein targets or global mRNA expression in CLL, few have attempted to characterise expression across the whole proteome. To achieve a non-biased, global proteomics characterisation, 14 CLL samples representing the genetic mutant subgroups NOTCH1, SF3B1 and WT, were subjected to quantitative mass spectrometry and compared with normal B cells using two isobaric tag experiments (TMT 10-plex). 6150 proteins were fully quantitated revealing a strong correlation between the regulated proteins across the CLL samples, independent of subtype. >800 proteins demonstrated significant upregulation (p<0.05) across the CLL samples. In addition to several novel cell surface markers, overexpressed proteins were strongly indicative of dysregulation to mRNA processing, spliceosome activity, transcriptional control by RNA pol II and epigenetic mechanisms (all p<10-10). A strong enrichment was observed for proteins coded by chromosome 12, often observed with trisomy in CLL (p<0.001). Downregulated proteins included cell adhesion molecules such as integrins and suggested a reduced capacity for endothelial transmigration (both p<10-10). These findings confirm many previous observations of CLL-specific protein overexpression (eg. CD5, ROR1, matriptase) and identify several novel surface targets for investigation. They also suggest that strong patterns of protein expression exist across CLL subtypes. Together, these results demonstrate the potential of proteomics and advocate the characterisation of further cancer samples by such methods.
HostingRepository	PRIDE
AnnounceDate	2018-01-26
AnnouncementXML	Submission_2018-01-26_03:59:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harvey Johnston
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; deamidated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-04-01 00:38:42	ID requested
⏵ 1	2018-01-26 03:59:39	announced

Johnston HE, Carter MJ, Larrayoz M, Clarke J, Garbis SD, Oscier D, Strefford JC, Steele AJ, Walewska R, Cragg MS, Proteomics Profiling of CLL Versus Healthy B-cells Identifies Putative Therapeutic Targets and a Subtype-independent Signature of Spliceosome Dysregulation. Mol Cell Proteomics, 17(4):776-791(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: CLL, TMT, Bridging Controls, whole cell, cancer, leukaemia

Spiro Garbis
contact affiliation	Cancer Sciences, Faculty of Medicine, University of Southampton, UK
contact email	s.d.garbis@soton.ac.uk
lab head
Harvey Johnston
contact affiliation	University of Southampton
contact email	h.johnston@soton.ac.uk
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/2018/01/PXD002004

PRIDE project URI

• PRIDE
  1. PXD002004
     1. Label: PRIDE project
     2. Name: Quantitative Proteomic Profiles of Chronic Lymphocytic Leukaemia