Down-regulation of MLL-AF9, MLL and MYC expression is not obligatory for monocyte-macrophage maturation in AML-M5 cell lines carrying t(9;11)(p22;q23)

Oncol Rep. 2006 Jan;15(1):207-11.

Abstract

The MLL-AF9 oncogene originates from the translocation t(9;11)(p22;q23), which is mainly associated with monocytic acute myeloid leukaemia (AML-M5; FAB-classification). In AML-M5 THP-1 cells carrying t(9;11) (p22;q23) and expressing MLL-AF9, we previously showed that MLL-AF9 expression is down-regulated during monocyte-macrophage maturation. We have subsequently observed that in a 'rapid-growing' variant of the THP-1 cell line (THP-1-R) MLL-AF9 down-regulation does not occur. MLL fusion proteins (including MLL-AF9) deregulate MYC transactivation activity, and both presence and absence of MYC down-regulation have been reported during monocyte-macrophage maturation in THP-1 cells. In the present study, we analyze the expression patterns of MLL-AF9, MLL wild-type and MYC after induction of monocyte-macrophage terminal differentiation in the AML-M5 cell lines, THP-1, THP-1-R, Mono-Mac-6 (MM6) and MOLM-13, all of which carry t(9;11)(p22;q23) and express MLL-AF9. RT-PCR analysis indicated that down-regulation of MLL-AF9, MLL or MYC is not necessary to abolish malignant phenotypes by induction of terminal monocyte-macrophage differentiation in leukaemic cells carrying t(9;11)(p22;q23).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics
  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, Pair 9 / genetics
  • Down-Regulation
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Leukemia, Monocytic, Acute / genetics*
  • Leukemia, Monocytic, Acute / immunology
  • Macrophages / cytology*
  • Monocytes / cytology*
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Proto-Oncogene Proteins c-myc / genetics*
  • Translocation, Genetic

Substances

  • KMT2A protein, human
  • MLL-AF9 fusion protein, human
  • MYC protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-myc
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase