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Validation of an LC‐MS based approach for profiling histones in chronic lymphocytic leukemia
Author(s) -
Su Xiaodan,
Lucas David M.,
Zhang Liwen,
Xu Hua,
Zabrouskov Vlad,
Davis Melanie E.,
Knapp Amy R.,
Young Donn C.,
Payne Philip R. O.,
Parthun Mark R.,
Marcucci Guido,
Grever Michael R.,
Byrd John C.,
Freitas Michael A.
Publication year - 2009
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200800333
Subject(s) - histone , epigenetics , chronic lymphocytic leukemia , chromatin , proteomics , biology , shotgun proteomics , computational biology , cancer research , microbiology and biotechnology , leukemia , genetics , gene
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.