Quantitative Proteomics to Characterize Specific Histone H2A Proteolysis in Chronic Lymphocytic Leukemia and the Myeloid THP-1 Cell Line

International Journal of Molecular Sciences

Pieter Glibert²  Liesbeth Vossaert²  Katleen Van Steendam²  Stijn Lambrecht³  Filip Van Nieuwerburgh²  Fritz Offner⁴  Thomas Kipps¹  Maarten Dhaenens² 

[1] Department of Medicine, Moores Cancer Center, University of California at San Diego (UCSD), 3855 Health Sciences Drive, La Jolla, CA 92093, USA; E-Mail:;Laboratory of Pharmaceutical Biotechnology, Ghent University, 72 Harelbekestraat, B-9000 Ghent, Belgium; E-Mails:;Department of Rheumatology, Ghent University Hospital, 185 1P7 De Pintelaan, B-9000 Ghent, Belgium; E-Mail:;Department of Hematology, Ghent University Hospital, 185 1P7 De Pintelaan, B-9000 Ghent, Belgium; E-Mail:

关键词: histone H2A;    proteolysis;    histone clipping;    chronic lymphocytic leukemia;    THP-1 cells;    quantitative proteomics;   

DOI  :  10.3390/ijms15069407

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2014 by the authors; licensee MDPI, Basel, Switzerland.