PXD006570

PXD006570 is an original dataset announced via ProteomeXchange.

Title	Aging-related proteome alterations in B cells may predispose for chronic lymphocytic leukemia - cytoplasmic proteins of elderly B cells
Description	Chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, is still incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. In order to get more detailed insights into CLL development, we performed a comprehensive proteome analysis of primary human CLL cells and B cells from young and age-matched healthy individuals. For comparison, we also analyzed the chronic B cell leukemia cell line JVM-13 showing rather limited similarity to the primary cells. A principal component analysis comprising 6945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and CLL patients. Remarkably, B cells from aged controls displayed significant regulation of proteins related to metabolic processes and stress response in mitochondria such as DLAT, FIS1 and NDUFAB1 as well as DNA repair including RAD9A, MGMT and XPA. Interestingly, these alterations apparently correlating with aging of B cells may also be essential for tumorigenesis and were observed similarly in CLL cells. In CLL cells, in addition, some remarkable unique features like the loss of tumor suppressor molecules PNN and JARID2, and high expression of CCDC88A, PIGR and ID3 otherwise associated with epithelial mesenchymal transition and stemness were determined. Furthermore, while typical hallmarks of cancer such as cell proliferation were hardly apparent for CLL cells, alterations of metabolic enzymes were another outstanding feature in comparison to normal B cells, indicating increased beta-oxidation of fatty acids and increased consumption of glutamine. Targeted metabolomics assays corroborated these results. The present findings identify previously unrecognized features of CLL cells and suggest that aging may be accompanied by proteome alterations functionally relevant for predisposing B cells to transform to CLL cells.
HostingRepository	PRIDE
AnnounceDate	2017-12-07
AnnouncementXML	Submission_2017-12-07_03:56:10.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD006570
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christopher Gerner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	residues isobaric at 128.058578 Da; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-23 05:28:23	ID requested
⏵ 1	2017-12-07 03:56:11	announced

Mayer RL, Schwarzmeier JD, Gerner MC, Bileck A, Mader JC, Meier-Menches SM, Gerner SM, Schmetterer KG, Pukrop T, Reichle A, Slany A, Gerner C, Proteomics and metabolomics identify molecular mechanisms of aging potentially predisposing for chronic lymphocytic leukemia. Mol Cell Proteomics, 17(2):290-303(2018) [pubmed]

submitter keyword: Chronic lymphocytic leukemia, primary human B lymphocytes, shotgun proteomics, aging, glutaminolysis, fatty acid beta oxidation, Q Exactive orbitrap

Christopher Gerner
contact affiliation	University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry
contact email	christopher.gerner@univie.ac.at
lab head
Christopher Gerner
contact affiliation	University of Vienna
contact email	christopher.gerner@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006570
     1. Label: PRIDE project
     2. Name: Aging-related proteome alterations in B cells may predispose for chronic lymphocytic leukemia - cytoplasmic proteins of elderly B cells