Emerging therapeutic targets in human acute myeloid leukemia (part 2) - bromodomain inhibition should be considered as a possible strategy for various patient subsets

被引:9
作者
Reikvam, Hakon [1 ,2 ]
Tuyen Thi van Hoang [2 ]
Bruserud, Oystein [1 ,2 ]
机构
[1] Haukeland Hosp, Dept Med, N-5021 Bergen, Norway
[2] Univ Bergen, Inst Clin Sci, Fac Med, Sect Hematol, Bergen, Norway
关键词
acetylation; acute myeloid leukemia; bromodomain; epigenetic; histone; methyl transferase; methylation; therapy; ACUTE MYELOGENOUS LEUKEMIA; ELONGATION COMPLEX SEC; NF-KAPPA-B; HISTONE ACETYLTRANSFERASE; GENE-EXPRESSION; AML CELLS; ANTIANGIOGENIC THERAPY; SELECTIVE-INHIBITION; KINASE INHIBITOR; HIGH-RISK;
D O I
10.1586/17474086.2015.1036025
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:315 / 327
页数:13
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