MLL-AF9 oncogene expression affects cell growth but not terminal differentiation and is downregulated during monocyte-macrophage maturation in AML-M5 THP-1 cells

Andrea Pession, Vincenzo Martino, Roberto Tonelli, Claudia Beltramini, Franco Locatelli, Giulia Biserni, Monica Franzoni, Francesea Freccero, Luca Montemurro, Laura Pattacini, Guido Paolucci

Research output: Contribution to journalArticle

Abstract

The MLL-AF9 oncogene - one of the most frequent MLL/HRX/ALL-1 rearrangements found in infantile and therapy-related leukaemias - originates from t(9;11) (p22;q23) and is mainly associated with monocytic acute myeloid leukaemia (AML-M5; FAB-classification). Here, we investigated the MLL-AF9 function by means of an antisense phosphorothioate-oligodeoxyribonucleotide (MLL-AF9-PS-ODNas) using the THP-1 AML-M5 cell line carrying t(9;11). Having confirmed that MLL-AF9-PS-ODNas induces strong inhibition of THP-1 cell growth, but only a moderate increase in apoptosis, we found that MLL-AF9-PS-ODNas did not induce morphofunctional terminal differentiation or restore M-CSF-, G-CSF- or GM-CSF-induced differentiation. Moreover, THP-1 cells showed the same phenotype with/without MLL-AF9-PS-ODNas. In THP-1 cells differentiated to mature macrophage-like cells by PMA/TPA or ATRA, MLL-AF9 expression was downregulated. Thus, in the monocytic lineage, MLL-AF9 may be expressed only in early phases and can induce deregulated amplification in both nonmalignant and malignant cells, maintaining the monocytic phenotype without blocking final maturation. Our findings suggest that: (1) as well as directly promoting cell growth, MLL-AF9 may also indirectly determine phenotype; (2) other leukaemogenic mutations associated with MLL-AF9-related leukaemias should be searched for mainly in processes of resistance to apoptosis (where MLL-AF9 may play only a limited role) and differentiation blockage (where MLL-AF9 may play no role).

Original languageEnglish
Pages (from-to)8671-8676
Number of pages6
JournalOncogene
Volume22
Issue number54
DOIs
Publication statusPublished - Nov 27 2003

Keywords

  • Cell growth
  • Differentiation
  • Expression
  • MLL-AF9
  • THP-1

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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  • Cite this

    Pession, A., Martino, V., Tonelli, R., Beltramini, C., Locatelli, F., Biserni, G., Franzoni, M., Freccero, F., Montemurro, L., Pattacini, L., & Paolucci, G. (2003). MLL-AF9 oncogene expression affects cell growth but not terminal differentiation and is downregulated during monocyte-macrophage maturation in AML-M5 THP-1 cells. Oncogene, 22(54), 8671-8676. https://doi.org/10.1038/sj.onc.1207125