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Int J Mol Sci. 2014 May 27;15(6):9407-21. doi: 10.3390/ijms15069407.

Quantitative proteomics to characterize specific histone H2A proteolysis in chronic lymphocytic leukemia and the myeloid THP-1 cell line.

Author information

1
Laboratory of Pharmaceutical Biotechnology, Ghent University, 72 Harelbekestraat, B-9000 Ghent, Belgium. pieter.glibert@ugent.be.
2
Laboratory of Pharmaceutical Biotechnology, Ghent University, 72 Harelbekestraat, B-9000 Ghent, Belgium. liesbeth.vossaert@ugent.be.
3
Laboratory of Pharmaceutical Biotechnology, Ghent University, 72 Harelbekestraat, B-9000 Ghent, Belgium. katleen.vansteendam@ugent.be.
4
Department of Rheumatology, Ghent University Hospital, 185 1P7 De Pintelaan, B-9000 Ghent, Belgium. stijn.lambrecht@hotmail.com.
5
Laboratory of Pharmaceutical Biotechnology, Ghent University, 72 Harelbekestraat, B-9000 Ghent, Belgium. filip.vannieuwerburgh@ugent.be.
6
Department of Hematology, Ghent University Hospital, 185 1P7 De Pintelaan, B-9000 Ghent, Belgium. fritz.offner@ugent.be.
7
Department of Medicine, Moores Cancer Center, University of California at San Diego (UCSD), 3855 Health Sciences Drive, La Jolla, CA 92093, USA. tkipps@ucsd.edu.
8
Laboratory of Pharmaceutical Biotechnology, Ghent University, 72 Harelbekestraat, B-9000 Ghent, Belgium. maarten.dhaenens@ugent.be.
9
Laboratory of Pharmaceutical Biotechnology, Ghent University, 72 Harelbekestraat, B-9000 Ghent, Belgium. dieter.deforce@ugent.be.

Abstract

Proteome studies on hematological malignancies contribute to the understanding of the disease mechanism and to the identification of new biomarker candidates. With the isobaric tag for relative and absolute quantitation (iTRAQ) method we analyzed the protein expression between B-cells of healthy people and chronic lymphocytic leukemia (CLL) B-cells. CLL is the most common lymphoid cancer of the blood and is characterized by a variable clinical course. By comparing samples of patients with an aggressive vs. indolent disease, we identified a limited list of differentially regulated proteins. The enhanced sensitivity attributed to the iTRAQ labels led to the discovery of a previously reported but still not clarified proteolytic product of histone H2A (cH2A) which we further investigated in light of the suggested functional properties of this modification. In the exploratory proteome study the Histone H2A peptide was up-regulated in CLL samples but a more specific and sensitive screening of a larger patient cohort indicated that cH2A is of myeloid origin. Our subsequent quantitative analysis led to a more profound characterization of the clipping in acute monocytic leukemia THP-1 cells subjected to induced differentiation.

PMID:
24871368
PMCID:
PMC4100102
DOI:
10.3390/ijms15069407
[Indexed for MEDLINE]
Free PMC Article

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