title: Understanding life and death decisions in human leukaemias.
abstract: Human leukaemia cells have an often unique ability to either undergo apoptotic cell death mechanisms or, at other times, undergo proliferative expansion, sometimes to the same stimulus such as the pluripotent cytokine TNFα (tumour necrosis factor α). This potential for life/death switching helps us to understand the molecular signalling machinery that underlies these cellular processes. Furthermore, looking at the involvement of these switching signalling pathways that may be aberrant in leukaemia informs us of their importance in cancer tumorigenesis and how they may be targeted pharmacologically to treat various types of human leukaemias. Furthermore, these important pathways may play a crucial role in acquired chemotherapy resistance and should be studied further to overcome in the clinic many drug-resistant forms of blood cancers. In the present article, we uncover the relationship that exists in human leukaemia life/death switching between the anti-apoptotic pro-inflammatory transcription factor NF-κB (nuclear factor κB) and the cytoprotective antioxidant-responsive transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2). We also discuss recent findings that reveal a major role for Btk (Bruton's tyrosine kinase) in both lymphocytic and myeloid forms of human leukaemias and lymphomas.
authors.affiliation: *Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, U.K.
authors.forename: David J
authors.initials: DJ
authors.lastname: MacEwan
authors.affiliation: *Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, U.K.
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Barrera
authors.affiliation: *Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, U.K.
authors.forename: Sujitra
authors.initials: S
authors.lastname: Keadsanti
authors.affiliation: †Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U.K.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Rushworth
authors.affiliation: *Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, U.K.
authors.forename: Niraj M
authors.initials: NM
authors.lastname: Shah
authors.affiliation: *Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, U.K.
authors.forename: Tianma
authors.initials: T
authors.lastname: Yuan
authors.affiliation: †Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U.K.
authors.forename: Lyubov
authors.initials: L
authors.lastname: Zaitseva
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human