title: Molecular studies reveal a MLL-MLLT3 gene fusion displaced in a case of childhood acute lymphoblastic leukemia with complex karyotype.
abstract: Rearrangement of the mixed lineage-leukemia gene (MLL-r) is common in hematological diseases and is generally associated with poor prognosis. The mixed-lineage leukemia gene translocated to, 3 (MLLT3) gene (9p22) is a frequent MLL-r partner (∼18% of leukemias with MLL rearrangement) and is characterized by the translocation t(9;11) (p22;q23), forming an MLL-MLLT3 gene fusion. MLL-r are usually simple reciprocal translocations between two different chromosomes, although karyotypes with complex MLL-r have been observed. We present a rare case of a child with acute lymphoblastic leukemia with a complex karyotype in which the classical t(9;11) (p22;q23) was cryptically relocated into a third chromosome in a balanced three-way translocation. At the genome level, however, the MLL-MLLT3 three-way translocation still displayed both reciprocal fusion transcripts. This argues in favor for a model where a simple two-way t(9;11) (p22;q23) was likely the first step that then evolved in to a more complex karyotype. Multicolor banding techniques can be used to greatly refine complex karyotypes and its chromosomal breakpoints. Also in the presence of putative new rearrangements, Long distance inverse-PCR is an important tool to identify which gene fusion is involved.
authors.affiliation: Clinical Medicine Postgraduate Program, College of Medicine, Federal University, Rio de Janeiro, Brazil; Cytogenetics Department, Bone Marrow Transplantation Unit, National Cancer Institute, Rio de Janeiro, Brazil.
authors.forename: Daniela Ribeiro
authors.initials: DR
authors.lastname: Ney Garcia
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.affiliation: Postgraduate Oncology Program, National Cancer Institute, Rio de Janeiro, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Emerenciano
authors.affiliation: Institute of Pharmaceutical Biology, Diagnostic Center of Acute Leukemia, Goethe-University of Frankfurt, Frankfurt/Main, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.affiliation: Institute of Pharmaceutical Biology, Diagnostic Center of Acute Leukemia, Goethe-University of Frankfurt, Frankfurt/Main, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.affiliation: Postgraduate Oncology Program, National Cancer Institute, Rio de Janeiro, Brazil.
authors.forename: Maria do Socorro
authors.initials: Mdo S
authors.lastname: Pombo-de-Oliveira
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.affiliation: Clinical Medicine Postgraduate Program, College of Medicine, Federal University, Rio de Janeiro, Brazil; Martagão Gesteira Institute of Pediatrics and Child Development, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcelo Gerardin
authors.initials: MG
authors.lastname: Poirot Land
authors.affiliation: Clinical Medicine Postgraduate Program, College of Medicine, Federal University, Rio de Janeiro, Brazil; Cytogenetics Department, Bone Marrow Transplantation Unit, National Cancer Institute, Rio de Janeiro, Brazil; Postgraduate Oncology Program, National Cancer Institute, Rio de Janeiro, Brazil. Electronic address: mlmacedosilva@hotmail.com.
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Macedo Silva
mesh_terms: D002675:Child, Preschool; D005260:Female; D006801:Humans; D059785:Karyotype; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C529663:MLL-MLLT3 fusion protein, human; D015514:Oncogene Proteins, Fusion
keywords: Acute lymphoblastic leukemia; MLL gene; complex karyotype; long-distance inverse polymerase chain reaction; molecular cytogenetics