Functional Unit of Haematology, Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy.
Leuk Res. 2011 Jul;35(7):921-31. doi: 10.1016/j.leukres.2011.01.033. Epub 2011 Mar 5.
Chronic myeloid leukaemia has a specific therapy: BCR/ABL inhibitor imatinib. Resistance due to BCR/ABL dependent and independent mechanisms is partially reversible by histone deacetylase inhibitors. We analysed by 2D-electrophoresis and anti-pan-acetylated and anti-phosphotyrosine immunoblots, followed by spot-matching and MALDI-TOF mass spectrometry, which proteome modifications would parallel restoration of sensitivity to imatinib by valproic acid (VPA). VPA plus imatinib significantly increased acetylation of HSP90 and hnRNP L and decreased phosphorylation of HSPs and hnRNPs in imatinib resistant cells. VPA was able to modify profoundly acetylome and phosphoproteome of CML cells, while reverting resistance to imatinib.
BCR/ABL 抑制剂伊马替尼。由于 BCR/ABL 依赖和独立的机制产生的耐药性可以部分通过组蛋白去乙酰化酶抑制剂逆转。我们通过 2D 电泳和抗泛乙酰化和抗磷酸酪氨酸免疫印迹进行分析，随后进行斑点匹配和 MALDI-TOF 质谱分析，以确定哪种蛋白质组修饰会与丙戊酸（VPA）恢复对伊马替尼的敏感性平行。VPA 加伊马替尼显著增加了伊马替尼耐药细胞中 HSP90 和 hnRNP L 的乙酰化，同时降低了 HSP 和 hnRNP 的磷酸化。VPA 能够深刻地修饰 CML 细胞的乙酰化组和磷酸化组，同时逆转对伊马替尼的耐药性。
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