Format

Send to

Choose Destination
Br J Haematol. 2019 Apr;185(1):65-78. doi: 10.1111/bjh.15751. Epub 2019 Jan 17.

Altered expression of metabolic pathways in CLL detected by unlabelled quantitative mass spectrometry analysis.

Author information

1
Discipline Molecular Medicine and Pathology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
2
Flinders Proteomic Facility, Department of Human Physiology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
3
Haematology, Molecular Medicine and Pathology, SA Pathology, Flinders Medical Centre, Adelaide, South Australia, Australia.

Abstract

Chronic lymphocytic leukaemia (CLL) remains the most common incurable malignancy of B cells in the western world. Patient outcomes are heterogeneous and can be difficult to predict with current prognostic markers. Here, we used a quantitative label-free proteomic technique to ascertain differences in the B-cell proteome from healthy donors and CLL patients with either mutated (M-CLL) or unmutated (UM-CLL) IGHV to identify new prognostic markers. In peripheral B-CLL cells, 349 (22%) proteins were differentially expressed between normal B cells and B-CLL cells and 189 (12%) were differentially expressed between M-CLL and UM-CLL. We also examined the proteome of proliferating CLL cells in the lymph nodes, and identified 76 (~8%) differentially expressed proteins between healthy and CLL lymph nodes. B-CLL cells show over-expression of proteins involved in lipid and cholesterol metabolism. A comprehensive lipidomic analysis highlighted large differences in glycolipids and sphingolipids. A shift was observed from the pro-apoptotic lipid ceramide towards the anti-apoptotic/chemoresistant lipid, glucosylceramide, which was more evident in patients with aggressive disease (UM-CLL). This study details a novel quantitative proteomic technique applied for the first time to primary patient samples in CLL and highlights that primary CLL lymphocytes display markers of a metabolic shift towards lipid synthesis and breakdown.

KEYWORDS:

CLL ; SWATH ; lipidomics; metabolism; proteomics

PMID:
30656643
DOI:
10.1111/bjh.15751

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center