Modification of histone acetylation and its regulation effect to the expression of mismatch repair genes in acute leukemia / 白血病·淋巴瘤

ABSTRACT

Objective To explore the status of histone acetylation modification and their regulatory effect to hMSH2 gene and hMLH1 gene expression in acute leukemia. Methods Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of hMSH2 and hMLH1 mRNA, and Western blot was used to measure the expression of histone H3, H4, HDACi, hMSH2 and hMLH1 protein in mononuclear cells of 56 acute leukemia patients and 30 healthy volunteers. The mononuclear cells of 30 acute leukemia patients were treated with histone deacetylase inhibitors trichostatin A (TSA), and measured the expression difference of histone H3, H4, HDAC1, hMSH2 and hMLH1 in the mononuclear cells treated with TSA. Results The protein expression levels of hMSH2, hMLH1, histone H3 and histone H4 in those mononuclear cells of acute leukemia patients were 0.4610±0.1211, 0.4013±0.1143, 0.4103±0.1241 and 0.4251±0.1081, respectively, which were significantly decreased comparing with those of healthy volunteers (0.9461±0. 1841, 0.996±0.2021, 0.8971±0. 1194 and 0.9513±0.1953) (t = 3.341, 3.935, 2.843 and 3.575,respectinely, P ＜0.05). The protein expression levels of HDAC1 (0.8841±0.2018) of acute leukemia patients was significantly increased comparing with those of healthy volunteers (0.5142±0.1340) (t= 2.634, P ＜0.05).After treatment with TSA for 48 hours, the protein expression of hMSH2 was increased nearly 1.5-fold, hMLH1 about 1.6-fold, H3 about 2.9-fold and H4 about 3.4-fold comparing with the negative control groups (P ＜0.05),while the protein expression of HDAC1 were decreased comparing with the negative control groups by 40 %.Conclusion There was an low expression phenomenon of histone acetylation in acute leukemia, and histone acetylation played an important role in regulation of the mismatch repair gene expression in acute leukemia.