title: Quantitative analysis of histone H3 and H4 post-translational modifications in doxorubicin-resistant leukemia cells.
abstract: The epigenetic remodeling of chromatin through histone modifications has been widely implicated in drug resistance of cancer cells. However, whether epigenetic mechanisms contribute specifically to doxorubicin resistance in leukemia has not been carefully examined. Using a stable and sensitive workflow based on LC-MS, we quantitatively compared the extents of methylation and acetylation of histone H3 and H4 in acute leukemia cell line HL60 and its doxorubicin-resistant derivative, HL60/ADR, as well as the chronic leukemia cell line K562 and its doxorubicin-resistant derivative, K562/ADR. We found that increased levels of H3K9 methylation, H3K14, H3K18 and H3K23 acetylation, and potentially H4K20 methylation, are associated with drug resistance in both cells. Our results demonstrated that the doxorubicin-resistant acute and chronic leukemia cell lines may share a common epigenetic mechanism that involves a combination of transcriptional activation and silencing.
authors: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.
authors: Tao
authors: T
authors: Liu
authors: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.|State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai Key Laboratory of Cell Engineering, Shanghai, China.
authors: Qingcheng
authors: Q
authors: Guo
authors: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.|State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai Key Laboratory of Cell Engineering, Shanghai, China.
authors: Huaizu
authors: H
authors: Guo
authors: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.|PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, Beijing, China.
authors: Sheng
authors: S
authors: Hou
authors: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.
authors: Jing
authors: J
authors: Li
authors: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.|PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, Beijing, China.
authors: Hao
authors: H
authors: Wang
mesh_terms: D000107:Acetylation; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006657:Histones / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics; D013058:Mass Spectrometry; D008745:Methylation; D011499:Protein Processing, Post-Translational
chemical_list: D000903:Antibiotics, Antineoplastic; D006657:Histones; D004317:Doxorubicin
keywords: LC-MS; doxorubicin resistance; histone modification; leukemia