title: Validation of an LC-MS based approach for profiling histones in chronic lymphocytic leukemia.
abstract: The in vitro evaluation of histones and their PTMs has drawn substantial interest in the development of epigenetic therapies. The differential expression of histone isoforms may serve as a potential marker in the classification of diseases affected by chromatin abnormalities. In this study, protein profiling by LC and MS was used to explore differences in histone composition in primary chronic lymphocytic leukemia (CLL) cells. Extensive method validations were performed to determine the experimental variances that would impact histone relative abundance. The resulting data demonstrated that the proposed methodology was suitable for the analysis of histone profiles. In 4 normal individuals and 40 CLL patients, a significant decrease in the relative abundance of histone H2A variants (H2AFL and H2AFA/M*) was observed in primary CLL cells as compared to normal B cells. Protein identities were determined using high mass accuracy MS and shotgun proteomics.
authors.affiliation: Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Su
authors.forename: David M
authors.initials: DM
authors.lastname: Lucas
authors.forename: Liwen
authors.initials: L
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Vlad
authors.initials: V
authors.lastname: Zabrouskov
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Davis
authors.forename: Amy R
authors.initials: AR
authors.lastname: Knapp
authors.forename: Donn C
authors.initials: DC
authors.lastname: Young
authors.forename: Philip R O
authors.initials: PR
authors.lastname: Payne
authors.forename: Mark R
authors.initials: MR
authors.lastname: Parthun
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Michael R
authors.initials: MR
authors.lastname: Grever
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Michael A
authors.initials: MA
authors.lastname: Freitas
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D015415:Biomarkers / Q000032:analysis; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000032:analysis* / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D006657:Histones; D020033:Protein Isoforms