title: Proteomic profiling identifies specific histone species associated with leukemic and cancer cells.
abstract: BACKGROUND
  Chromatin is an extraordinarily complex structure. Much of this complexity results from the presence of numerous histone post-translational modifications and histone variants. Alterations in the patterns of histone post-translational modifications are emerging as a feature of many types of cancer and have been shown to have prognostic value.
  
  
  RESULTS
  We have applied a liquid chromatography/mass spectrometry-based approach to comprehensively characterize the histone proteome in primary samples from chronic lymphocytic leukemia (CLL) patients, as well as bladder and breast cancer cell culture models. When compared to non-malignant CD19+ B cells from healthy donors, the CLL histone proteome showed a distinct signature of differentially expressed species, spanning all the histones studied and including both post-translationally modified species and unmodified, non-allelic replication-dependent histone isoforms. However, the large changes in histone H3 and H4 that are characteristic of many cancer types were not observed. One of species of H2A (mass = 14,063 Da) was the most strongly associated with time to treatment in CLL patients. CLL patient samples also demonstrated histone profiles that were distinct from those of the bladder and breast cancer cells.
  
  
  CONCLUSIONS
  Signatures of histone profiles are complex and can distinguish between healthy individuals and CLL patients and may provide prognostic markers. In addition, histone profiles may define tissue specific malignancies.
authors: Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210 USA.
authors: Rajbir
authors: R
authors: Singh
authors: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210 USA.
authors: Sean W
authors: SW
authors: Harshman
authors: Department of Internal Medicine, The Ohio State University, Columbus, OH 43210 USA.
authors: Amy S
authors: AS
authors: Ruppert
authors: Department of Internal Medicine, The Ohio State University, Columbus, OH 43210 USA.
authors: Amir
authors: A
authors: Mortazavi
authors: Department of Internal Medicine, The Ohio State University, Columbus, OH 43210 USA ; Division of Medicinal Chemistry in the College of Pharmacy, The Ohio State University, Columbus, OH 43210 USA.
authors: David M
authors: DM
authors: Lucas
authors: Department of Internal Medicine, The Ohio State University, Columbus, OH 43210 USA.
authors: Jennifer M
authors: JM
authors: Thomas-Ahner
authors: Department of Internal Medicine, The Ohio State University, Columbus, OH 43210 USA.
authors: Steven K
authors: SK
authors: Clinton
authors: Department of Internal Medicine, The Ohio State University, Columbus, OH 43210 USA.
authors: John C
authors: JC
authors: Byrd
authors: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210 USA.
authors: Michael A
authors: MA
authors: Freitas
authors: Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210 USA.
authors: Mark R
authors: MR
authors: Parthun
keywords: Chromatin; Chronic lymphocytic leukemia; Histone; Post-translational modification