School of Medicine, New York University, NY, USA.
Expert Rev Hematol. 2010 Apr;3(2):187-203. doi: 10.1586/ehm.10.9.
Cutaneous T-cell lymphomas (CTCLs) are rare lymphomas that arise primarily in the skin and are treated with skin-directed therapies in early-stage disease. Systemic therapy is indicated once skin-directed therapy is ineffective or for advanced-stage disease. CTCLs tend to be poorly responsive to chemotherapy and are incurable except for allogeneic stem cell transplantation. Recently, a new class of agents called histone deacetyalse inhibitors (HDACis) have shown remarkable activity in T-cell lymphomas in general and CTCLs in particular. Oral vorinostat and intravenous romidepsin are two HDACis that are now approved by the US FDA for use in patients with relapsed CTCLs. Several other HDACis are currently in clinical trials for CTCLs and other diseases and, although these agents vary by chemical structure and potency, the results of the ongoing clinical trials will eventually reveal if there are differences in clinical activity as well. The exact mechanism of action of these agents is unknown, but they are thought to affect the acetylation status of histones and other proteins in the cell and epigentically modulate transcription and other cellular activities. This leads to a myriad of downstream effects on cell cycle, apoptosis and differentiation. The following review summarizes the known biological mechanisms and clinical activity of various HDACis in the treatment of CTCLs and tries to define their role in the treatment paradigm of these unusual disorders.
皮肤 T 细胞淋巴瘤（CTCLs）是一种罕见的淋巴瘤，主要发生在皮肤中，在疾病早期采用皮肤靶向治疗。一旦皮肤靶向治疗无效或疾病处于晚期，则需要采用系统治疗。CTCLs 对化疗的反应通常较差，除了异基因干细胞移植外，无法治愈。最近，一类称为组蛋白去乙酰化酶抑制剂（HDACis）的新型药物在一般 T 细胞淋巴瘤和 CTCL 中表现出显著的活性。口服伏立诺他和静脉注射罗米地辛是两种目前已被美国 FDA 批准用于治疗复发性 CTCL 的 HDACis。目前还有其他几种 HDACis 正在临床试验中用于 CTCL 和其他疾病，尽管这些药物在化学结构和效力上有所不同，但正在进行的临床试验的结果最终将揭示它们在临床活性方面是否存在差异。这些药物的确切作用机制尚不清楚，但它们被认为会影响细胞中组蛋白和其他蛋白质的乙酰化状态，并通过表观遗传方式调节转录和其他细胞活动。这会导致细胞周期、凋亡和分化的无数下游效应。以下综述总结了各种 HDACis 在治疗 CTCL 中的已知生物学机制和临床活性，并试图确定它们在这些异常疾病治疗模式中的作用。
