title: Cryptic MLL-AF10 fusion caused by insertion of duplicated 5' part of MLL into 10p12 in acute leukemia: a case report.
abstract: Chromosomal translocations involving the mixed lineage leukemia gene (MLL) located at 11q23 belong to common chromosomal abnormalities in both acute lymphoblastic (ALL) and acute myeloid leukemias (AML). It has been suggested that the mechanism of MLL leukemogenesis might be a result of a gain-of-function effect of the MLL fusion gene and simultaneous loss of function of one of the MLL alleles (haploinsufficiency). One of the recurrent translocations in AML-M5 involves chromosomal locus 10p12 and results in the MLL-AF10 fusion gene. Several mechanisms leading to MLL-AF10 fusion have been reported, and they have involved rearrangement of the 11q23 region. We present a detailed structural analysis of an AML case with an extra copy of the 5' part of MLL region and its insertion into the short arm of chromosome 10, resulting in an MLL-AF10 fusion without rearrangement of the MLL alleles on both chromosomes 11. Our observation supports a role for a simple MLL gain-of-function in leukemogenesis.
authors.affiliation: Department of Hemato-oncology, Palacky University Hospital, Olomouc, Czech Republic. marie.jarosova@fnol.cz
authors.forename: Marie
authors.initials: M
authors.lastname: Jarosova
authors.forename: Sylvia
authors.initials: S
authors.lastname: Takacova
authors.forename: Milena
authors.initials: M
authors.lastname: Holzerova
authors.forename: Monika
authors.initials: M
authors.lastname: Priwitzerova
authors.forename: Martina
authors.initials: M
authors.lastname: Divoka
authors.forename: Ilona
authors.initials: I
authors.lastname: Lakoma
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mihal
authors.forename: Karel
authors.initials: K
authors.lastname: Indrak
authors.forename: Vladimir
authors.initials: V
authors.lastname: Divoky
mesh_terms: D015139:Blotting, Southern; D002675:Child, Preschool; D002879:Chromosomes, Human, Pair 10; D020440:Gene Duplication; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*
chemical_list: C497422:KMT2A protein, human; C470550:MLL-AF10 fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase