Proteomics-based strategies to identify proteins relevant to chronic lymphocytic leukemia

Alsagaby, Suliman A., Khanna, Sanjay, Hart, Keith, Pratt, Guy, Fegan, Christopher ORCID: https://orcid.org/0000-0001-9685-0621, Pepper, Christopher, Brewis, Ian and Brennan, Paul ORCID: https://orcid.org/0000-0001-8792-0499 2014. Proteomics-based strategies to identify proteins relevant to chronic lymphocytic leukemia. Journal of Proteome Research 13 (11) , pp. 5051-5062. 10.1021/pr5002803

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Abstract

Chronic lymphocytic leukemia (CLL), a malignant B-cell disorder, is characterized by a heterogeneous clinical course. Two-dimensional nano liquid chromatography (2D-nano–LC) coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) (LC–MALDI) was used to perform qualitative and quantitative analysis on cellular extracts from 12 primary CLL samples. We identified 728 proteins and quantified 655 proteins using isobaric tag-labeled extracts. Four strategies were used to identify disease-related proteins. First, we integrated our CLL proteome with published gene expression data of normal B-cells and CLL cells to highlight proteins with preferential expression in the transcriptome of CLL. Second, as CLL’s outcome is heterogeneous, our quantitative proteomic data were used to indicate heterogeneously expressed proteins. Third, we used the quantitative data to identify proteins with differential abundance in poor prognosis CLL samples. Fourth, hierarchical cluster analysis was applied to identify hidden patterns of protein expression. These strategies identified 63 proteins, and 4 were investigated in a CLL cohort (39 patients). Thyroid hormone receptor-associated protein 3, T-cell leukemia/lymphoma protein 1A, and S100A8 were associated with high-risk CLL. Myosin-9 exhibited reduced expression in CLL samples from high-risk patients. This study shows the usefulness of proteomic approaches, combined with transcriptomics, to identify disease-related proteins.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	American Chemical Society
ISSN:	1535-3893
Last Modified:	17 Nov 2022 05:03
URI:	https://orca.cardiff.ac.uk/id/eprint/79024

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