Acetylome and phosphoproteome modifications in imatinib resistant chronic myeloid leukaemia cells treated with valproic acid

作者：Buchi Francesca; Pastorelli Roberta; Ferrari Germano; Spinelli Elena; Gozzini Antonella; Sassolini Francesca; Bosi Alberto; Tombaccini Donatella; Santini Valeria^*

来源：Leukemia Research, 2011, 35(7): 921-931.

DOI：10.1016/j.leukres.2011.01.033

• CML BCR/ABL
• Proteomics
• Imatinib resistance
• Valproic acid
• Protein phosphorylation
• Protein acetylation

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.

• 出版日期2011-7