title: Down-regulation of HOXA4, HOXA7, HOXA10, HOXA11 and MEIS1 during monocyte-macrophage differentiation in THP-1 cells.
abstract: The translocation t(9;11)(p22;q23) generates the MLL-AF9 oncogene and is commonly associated with monocytic acute myeloid leukemia (AML-M5; FAB-classification). For the oncogenicity of MLL-AF9, the (over)expression of several other genes, including selected HOXA cluster genes as well as MEIS1 (a HOX cofactor), is required. We previously showed that the down-regulation of MLL-AF9 expression is not obligatory for monocyte-macrophage maturation in AML-M5 cells carrying t(9;11)(p22;q23). In this study, we analyzed the expression patterns of HOXA4, 5, 6, 7, 9, 10 and 11 (defined as 'HOXA-code' genes) and MEIS1 by semiquantitative RT-PCR during the monocyte-macrophage differentiation induced by phorbol 12-myristate 13-acetate (PMA) in THP-1 cells carrying t(9;11)(p22;q23) and expressing MLL-AF9. The analyses were performed in THP-1 cells expressing MLL-AF9 even after PMA treatment. The results showed that all the analyzed genes were expressed in untreated THP-1 cells. After the induction of differentiation, we observed a down-regulation of HOXA4, 7, 10, 11 and MEIS1, an up-regulation of HOXA6, and no significant variation in the expression of HOXA5 and 9. These data indicate that the expression of most HOXA-code genes, as well as MEIS1, could be implicated in the differentiation blockage observed in MLL-AF9-related leukemias.
authors.affiliation: Department of Pathology and Experimental Medicine, University of Parma, I-43100 Parma, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Martino
authors.forename: Annalisa
authors.initials: A
authors.lastname: Bianchera
authors.forename: Laura
authors.initials: L
authors.lastname: Reia
authors.forename: Ovidio
authors.initials: O
authors.lastname: Bussolati
authors.forename: Raffaella
authors.initials: R
authors.lastname: Fazzina
authors.forename: Flora
authors.initials: F
authors.lastname: Marino
authors.forename: Luca
authors.initials: L
authors.lastname: Montemurro
authors.forename: Roberto
authors.initials: R
authors.lastname: Tonelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Gazzola
authors.forename: Roberto
authors.initials: R
authors.lastname: Sala