title: 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).
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).
authors.affiliation: Department of Paediatrics, University of Bologna, Policlinico S. Orsola-Malpighi, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Martino
authors.forename: Roberto
authors.initials: R
authors.lastname: Tonelli
authors.forename: Luca
authors.initials: L
authors.lastname: Montemurro
authors.forename: Monica
authors.initials: M
authors.lastname: Franzoni
authors.forename: Flora
authors.initials: F
authors.lastname: Marino
authors.forename: Raffaella
authors.initials: R
authors.lastname: Fazzina
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015536:Down-Regulation; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics* / Q000276:immunology; D008264:Macrophages / Q000166:cytology*; D009000:Monocytes / Q000166:cytology*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C497422:KMT2A protein, human; C474558:MLL-AF9 fusion protein, human; C489427:MYC protein, human; D015514:Oncogene Proteins, Fusion; D016271:Proto-Oncogene Proteins c-myc; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase