title: FUS expression alters the differentiation response to all-trans retinoic acid in NB4 and NB4R2 cells.
abstract: The FUS gene is overexpressed in acute myeloid leukaemia (AML) patients and has roles in transcription and mRNA processing. We used ectopic expression of FUS and FUS antisense sequences to assess the effect of modulation of FUS expression in all-trans retinoic acid (ATRA)-sensitive (NB4) and insensitive (NB4R2) human acute promyelocytic (APL) cell lines which express the t(15:17) translocation. Growth, viability and differentiation patterns were maintained, but the expression of the FUS antisense construct in both the cell lines altered the response to ATRA: the previously ATRA-sensitive NB4 cells exhibited resistance; whilst the previously resistant NB4R2 cells showed a differentiation response to treatment.
authors.affiliation: Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Walsby
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Gilkes
authors.forename: Alex
authors.initials: A
authors.lastname: Tonks
authors.forename: Richard L
authors.initials: RL
authors.lastname: Darley
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Mills
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D034702:RNA-Binding Protein FUS / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods; D014178:Translocation, Genetic; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D016376:Oligonucleotides, Antisense; D034702:RNA-Binding Protein FUS; D014212:Tretinoin