Proteomic profiling identifies specific histone species associated with leukemic and cancer cells

蛋白质组学分析可识别与白血病和癌细胞相关的特定组蛋白种类

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作者:Rajbir Singh, Sean W Harshman, Amy S Ruppert, Amir Mortazavi, David M Lucas, Jennifer M Thomas-Ahner, Steven K Clinton, John C Byrd, Michael A Freitas, Mark R Parthun

Background

Chromatin is an extraordinarily complex structure. Much of this complexity

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.

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.

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