The Role of HDACs as Leukemia Therapy Targets using HDI.

Ahmad Ahmadzadeh, Elahe Khodadi, Mohammad Shahjahani, Jessika Bertacchini, Tina Vosoughi, Najmaldin Saki
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Abstract

Histone deacetylases (HDACs) are the enzymes causing deacetylation of histone and non-histone substrates. Histone deacetylase inhibitors (HDIs) are a family of drugs eliminating the effect of HDACs in malignant cells via inhibition of HDACs. Due to extensive effects upon gene expression through interference with fusion genes and transcription factors, HDACs cause proliferation and migration of malignant cells, inhibiting apoptosis in these cells via tumor suppressor genes. Over expression evaluation of HDACs in leukemias may be a new approach for diagnosis of leukemia, which can present new targets for leukemia therapy. HDIs inhibit HDACs, increase acetylation in histones, cause up- or down regulation in some genes and result in differentiation, cell cycle arrest and apoptosis induction in malignant cells via cytotoxic effects. Progress in identification of new HDIs capable of tracking several targets in the cell can result in novel achievements in treatment and increase survival in patients. In this review, we examine the role of HDACs as therapeutic targets in various types of leukemia as well as the role of HDIs in inhibition of HDACs for treatment of these malignancies.

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HDAC作为使用HDI的白血病治疗靶点的作用。
组蛋白脱乙酰酶(HDAC)是引起组蛋白和非组蛋白底物脱乙酰的酶。组蛋白脱乙酰酶抑制剂(HDIs)是一类通过抑制HDAC来消除HDAC在恶性细胞中的作用的药物。由于HDAC通过干扰融合基因和转录因子对基因表达的广泛影响,HDAC引起恶性细胞的增殖和迁移,通过肿瘤抑制基因抑制这些细胞的凋亡。HDAC在白血病中的过表达评估可能是诊断白血病的一种新方法,为白血病治疗提供新的靶点。HDIs抑制HDAC,增加组蛋白的乙酰化,引起某些基因的上调或下调,并通过细胞毒性作用导致恶性细胞分化、细胞周期停滞和凋亡诱导。在识别能够追踪细胞中几个靶点的新HDI方面取得进展,可以在治疗和提高患者生存率方面取得新的成就。在这篇综述中,我们研究了HDAC作为各种类型白血病的治疗靶点的作用,以及HDIs在抑制HDAC治疗这些恶性肿瘤中的作用。
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