Reikvam Håkon, Hoang Tuyen Thi van, Bruserud Øystein
Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Expert Rev Hematol. 2015 Jun;8(3):315-27. doi: 10.1586/17474086.2015.1036025. Epub 2015 Apr 22.
The recent advances in our understanding of leukemogenesis have clearly demonstrated that human acute myeloid leukemia is a heterogeneous malignancy, and several disease mechanisms should probably be regarded as possible therapeutic targets only for specific subsets of patients and not for acute myeloid leukemia in general. One promising strategy for epigenetic targeting is inhibition of the binding between bromodomain-containing transcription regulators and acetylated lysine residues on histones. This possible approach has been investigated especially for patients with 11q23 and chromosome 8 abnormalities. An alternative target is the histone methyltransferase COT1L. Major challenges for both approaches will be to clarify how these strategies should be combined with each other or with conventional chemotherapy, and whether their use should be limited to certain subsets of patients.
我们对白血病发生机制认识的最新进展清楚地表明，人类急性髓系白血病是一种异质性恶性肿瘤，几种疾病机制可能仅对特定患者亚群而言是潜在的治疗靶点，而非针对整个急性髓系白血病患者群体。表观遗传靶向治疗的一个有前景的策略是抑制含溴结构域的转录调节因子与组蛋白上乙酰化赖氨酸残基之间的结合。这种可能的方法尤其针对有11q23和8号染色体异常的患者进行了研究。另一个靶点是组蛋白甲基转移酶COT1L。这两种方法面临的主要挑战将是阐明这些策略应如何相互结合或与传统化疗相结合，以及它们的使用是否应局限于特定患者亚群。
