title: HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line.
abstract: BACKGROUND
  Homeobox (HOX) genes deregulation has been largely implicated in the development of human leukemia. Among the HOXB cluster, HOXB1 was silent in a number of analyzed acute myeloid leukemia (AML) primary cells and cell lines, whereas it was expressed in normal terminally differentiated peripheral blood cells.
  
  
  METHODS
  We evaluated the biological effects and the transcriptome changes determined by the retroviral transduction of HOXB1 in the human promyelocytic cell line HL60.
  
  
  RESULTS
  Our results suggest that the enforced expression of HOXB1 reduces cell growth proliferation, inducing apoptosis and cell differentiation along the monocytic and granulocytic lineages. Accordingly, gene expression analysis showed the HOXB1-dependent down-regulation of some tumor promoting genes, paralleled by the up-regulation of apoptosis- and differentiation-related genes, thus supporting a tumor suppressor role for HOXB1 in AML. Finally, we indicated HOXB1 promoter hypermethylation as a mechanism responsible for HOXB1 silencing.
  
  
  CONCLUSIONS
  We propose HOXB1 as an additional member of the HOX family with tumour suppressor properties suggesting a HOXB1/ATRA combination as a possible future therapeutic strategy in AML.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome 00161, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Petrini
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome 00161, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Felicetti
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome 00161, Italy.
authors.forename: Lisabianca
authors.initials: L
authors.lastname: Bottero
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome 00161, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Errico
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome 00161, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Morsilli
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome 00161, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Boe
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome 00161, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: De Feo
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome 00161, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carè