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 monocytemacrophage 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.

Down-regulation of HOXA4, HOXA7, HOXA10, HOXA11 and MEIS1 during monocyte-macrophage differentiation in THP-1 cells / MARTINO V; BIANCHERA A; REIA L; BUSSOLATI O; FAZZINA R; MARINO F; MONTEMURRO L; TONELLI R; PESSION A; GAZZOLA GC; SALA R. - In: MOLECULAR MEDICINE REPORTS. - ISSN 1791-2997. - 2:(2009), pp. 241-244. [10.3892/mmr]

Down-regulation of HOXA4, HOXA7, HOXA10, HOXA11 and MEIS1 during monocyte-macrophage differentiation in THP-1 cells

BIANCHERA, Annalisa;BUSSOLATI, Ovidio;GAZZOLA, Giancarlo;SALA, Roberto
2009

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 monocytemacrophage 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.
Down-regulation of HOXA4, HOXA7, HOXA10, HOXA11 and MEIS1 during monocyte-macrophage differentiation in THP-1 cells / MARTINO V; BIANCHERA A; REIA L; BUSSOLATI O; FAZZINA R; MARINO F; MONTEMURRO L; TONELLI R; PESSION A; GAZZOLA GC; SALA R. - In: MOLECULAR MEDICINE REPORTS. - ISSN 1791-2997. - 2:(2009), pp. 241-244. [10.3892/mmr]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/1915013
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