PXD001515

PXD001515 is an original dataset announced via ProteomeXchange.

Title	CLL iTRAQ2
Description	The mutational status of the immunoglobulin heavy chain variable region (IGHV) defines two clinically distinct forms of chronic lymphocytic leukemia (CLL) known as mutated (M-CLL) and un-mutated (UM-CLL). To elucidate the molecular mechanisms underlying the adverse clinical outcome associated with UM-CLL, total proteomes from 9 UM-CLL and 9 M-CLL samples were analysed by isobaric tags for relative and absolute quantification (iTRAQ)-based mass spectrometry. Unsupervised clustering, based on the expression of 3521 identified proteins, separated CLL samples into two groups corresponding to IGHV mutational status. Computational analysis showed that 43 cell migration/adhesion pathways were significantly enriched by 39 differentially expressed proteins, 35 of which were expressed at significantly lower levels in UM-CLL samples. Furthermore, UM-CLL cells under-expressed proteins associated with cytoskeletal remodelling and over-expressed proteins associated with transcriptional and translational activity. Taken together, our findings indicated that UM-CLL cells are less migratory and more adhesive than M-CLL cells, resulting in their retention in lymph nodes where they are exposed to proliferative stimuli. In keeping with this hypothesis, analysis of an extended cohort of 120 CLL patients revealed a strong and specific association between UM-CLL and lymphadenopathy. Our study illustrates the potential of total proteome analysis to elucidate pathogenetic mechanisms in cancer.
HostingRepository	PRIDE
AnnounceDate	2016-06-27
AnnouncementXML	Submission_2016-06-27_07:04:08.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rosalind Jenkins
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iTRAQ8plex-116 reporter+balance reagent acylated residue; methylthiolated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2014-11-19 06:00:56	ID requested
⏵ 1	2016-06-27 07:04:10	announced

Eagle GL, Zhuang J, Jenkins RE, Till KJ, Jithesh PV, Lin K, Johnson GG, Oates M, Park K, Kitteringham NR, Pettitt AR, Total proteome analysis identifies migration defects as a major pathogenetic factor in immunoglobulin heavy chain variable region (IGHV)-unmutated chronic lymphocytic leukemia. Mol Cell Proteomics, 14(4):933-45(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, iTRAQ, leukemia, mutation

Rosalind Elspeth Jenkins
contact affiliation	MRC Centre for Drug Safety Science, Dept Molecular and Clincal Pharmacology, University of Liverpool
contact email	R.Jenkins@liv.ac.uk
lab head
Rosalind Jenkins
contact affiliation	University of Liverpool
contact email	R.Jenkins@liv.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/2016/06/PXD001515

PRIDE project URI

• PRIDE
  1. PXD001515
     1. Label: PRIDE project
     2. Name: CLL iTRAQ2