Savlı Hakan, Galimberti Sara, Sünnetçi Deniz, Canesastraro Martina, Palumbo Giuseppe, Nagy Balint, Di Raimondo Francesco, Petrini Mario
Turk J Haematol. 2015 Sep;32(3):206-12. doi: 10.4274/tjh.2014.0058.
We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39.
Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR.
Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings.
Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS.
我们旨在了解硼替佐米和三氧化二砷对骨髓单核细胞系P39治疗所影响的分子途径。
使用寡核苷酸微阵列平台进行基因表达和途径分析。采用定量实时PCR进行验证研究。
硼替佐米治疗显示DIABLO和NF-κBIB（一种NF-κB抑制剂）上调，NF-κB1、NF-κB2和BIRC1基因表达下调。两种化合物联合治疗显示基因表达失调与单一硼替佐米治疗结果一致。特别是，P53是一个修饰更显著的途径，并且一个基因网络集中在β-雌二醇基因周围。β-雌二醇、BRCA2和FOXA1基因在我们的研究结果中出现显著失调。
结果支持关于蛋白酶体抑制剂可能用于治疗高危骨髓增生异常综合征（MDS）的建议。NF-κB被视为MDS白血病转化中的重要调节因子。
