MassIVE MSV000082941

Imported Reanalysis Dataset Public PXD006571

Aging-related proteome alterations in B cells may predispose for chronic lymphocytic leukemia - nuclear proteins of elderly B cells

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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. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Chronic lymphocytic leukemia ; primary human B lymphocytes ; shotgun proteomics ; aging ; glutaminolysis ; fatty acid beta oxidation ; Q Exactive orbitrap

Contact

Principal Investigators:
(in alphabetical order) 		Christopher Gerner, University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry, N/A
Submitting User: ccms

Publications

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. 2018 Feb;17(2):290-303. Epub 2017 Dec 1.

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