title: Emerging therapeutic targets in human acute myeloid leukemia (part 2) - bromodomain inhibition should be considered as a possible strategy for various patient subsets.
abstract: 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.
authors.affiliation: Department of Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Håkon
authors.initials: H
authors.lastname: Reikvam
authors.forename: Tuyen Thi van
authors.initials: TT
authors.lastname: Hoang
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002869:Chromosome Aberrations / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D011485:Protein Binding / Q000187:drug effects; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D014157:Transcription Factors
keywords: acetylation; acute myeloid leukemia; bromodomain; epigenetic; histone; methyl transferase; methylation; therapy