title: Farnesyltransferase inhibitors: molecular evidence of therapeutic efficacy in acute lymphoblastic leukemia through cyclin D1 inhibition.
abstract: BACKGROUND
  Farnesyltransferase inhibitors have the ability to interfere with various intracellular pathways, reducing cell survival and proliferation. They have become an attractive tool for cancer therapy, namely acute leukemias. In this work, we have studied the efficacy of α-hydroxyfarnesylphosphonic acid (α-HFPA) in CEM (acute T-cell lymphoblastic leukemia) in culture.
  
  
  METHODS
  CEM cells were incubated with α-HFPA at different concentrations; viability and proliferation studies were performed using the trypan blue exclusion assay and cell morphological analysis. Expression of lamin A/C, cyclin D1 and BAD were analyzed by flow cytometry.
  
  
  RESULTS
  Our results show that α-HFPA significantly decreases Farnesyltransferase activity, reduces cell proliferation and induces cell death through apoptosis in CEM cells, which is correlated with a reduction of cyclin D1 levels.
  
  
  CONCLUSIONS
  This study suggests that α-HFPA blocks the cell cycle and induces cell death through apoptosis in CEM cells and may be a therapeutic approach in ALL.
authors.affiliation: Applied Molecular Biology and Hematology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Carlos Bruno
authors.initials: CB
authors.lastname: Costa
authors.forename: João
authors.initials: J
authors.lastname: Casalta-Lopes
authors.forename: Carlos
authors.initials: C
authors.lastname: Andrade
authors.forename: Diana
authors.initials: D
authors.lastname: Moreira
authors.forename: Ana
authors.initials: A
authors.lastname: Oliveira
authors.forename: Ana C
authors.initials: AC
authors.lastname: Gonçalves
authors.forename: Vera
authors.initials: V
authors.lastname: Alves
authors.forename: Teresa
authors.initials: T
authors.lastname: Silva
authors.forename: Marília
authors.initials: M
authors.lastname: Dourado
authors.forename: José M
authors.initials: JM
authors.lastname: Nascimento-Costa
authors.forename: Ana B
authors.initials: AB
authors.lastname: Sarmento-Ribeiro
mesh_terms: D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005204:Farnesol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D063065:Organophosphonates / Q000494:pharmacology*; D010757:Phosphorous Acids; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C080570:(alpha-hydroxyfarnesyl)phosphonic acid; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D010757:Phosphorous Acids; D019938:Cyclin D1; D005204:Farnesol; D051231:Farnesyltranstransferase