title: Emerging therapeutic targets for the treatment of human acute myeloid leukemia (part 1) - gene transcription, cell cycle regulation, metabolism and intercellular communication.
abstract: Human acute myeloid leukemia is a heterogeneous disease and the effect of therapeutic targeting of specific molecular mechanisms will probably vary between patient subsets. Cell cycle regulators are among the emerging targets (e.g., aurora and polo-like kinases, cyclin-dependent kinases). Inhibition of communication between acute myeloid leukemia and stromal cells is also considered; among the most promising of these strategies are inhibition of hedgehog-initiated, CXCR4-CXCL12 and Axl-Gas6 signaling. Finally, targeting of energy and protein metabolism is considered, the most promising strategy being inhibition of isocitrate dehydrogenase in patients with IDH mutations. Thus, several strategies are now considered, and a major common challenge for all of them is to clarify how they 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: Michelle
authors.initials: M
authors.lastname: Hauge
authors.forename: Annette K
authors.initials: AK
authors.lastname: Brenner
authors.forename: Kimberley Joanne
authors.initials: KJ
authors.lastname: Hatfield
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D053823:Hedgehog Proteins; D047428:Protein Kinase Inhibitors; D007521:Isocitrate Dehydrogenase
keywords: CXCL12; acute myeloid leukemia; cell cycle; clinical studies; hedgehog signaling; isocitrate dehydrogenase; mesenchymal stem cell