title: Proteomics in acute myelogenous leukaemia (AML): methodological strategies and identification of protein targets for novel antileukaemic therapy.
abstract: Enduring efforts into determination of the molecular biological status of acute myelogenous leukaemia (AML), a stem cell disease characterised by distinct blastic differentiation blocks and their extensive growth, continue to provide us with prognostically important information for more than half of all patients. In subsets of AML, molecular diagnostics rigorously guide the clinician toward the choice of optimal therapy. The in-depth characterization of leukemogenesis associated genetic alterations, such as the combined presence of activating mutations of tyrosine kinases together with altered transcription factors, and the documented impact of these mutations upon prognosis of AML, suggests AML as a primary candidate for pioneering proof-of-principle studies with new high throughput protein analysis techniques. This review aims to introduce the reader to proteomic methodology, e.g. two-dimensional polyacrylamide gel electrophoresis, mass spectrometry, SELDI and protein arrays. Examples of its use, including single cell phosphoprotein profiling in risk stratification, the probing of cellular effects of conventional chemotherapeutics and novel target determination are presented. Based on original proteomic analysis of AML, molecular characteristics of AML, in addition to knowledge of conventional therapeutics and novel drugs, we attempt to forecast the influence of proteomics in therapy development for AML.
authors.affiliation: Institute of Medicine, Hematology Section, University of Bergen and Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway. Bjorn.Gjertsen@med.uib.no.
authors.forename: Gry
authors.initials: G
authors.lastname: Sjøholt
authors.forename: Nina
authors.initials: N
authors.lastname: Anensen
authors.forename: Line
authors.initials: L
authors.lastname: Wergeland
authors.forename: Emmet
authors.initials: E
authors.lastname: Mc Cormack
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
mesh_terms: D000107:Acetylation; D017209:Apoptosis; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006657:Histones / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism*; D013058:Mass Spectrometry; D009363:Neoplasm Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors*; D040081:Protein Array Analysis; D040901:Proteomics; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D006657:Histones; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53