title: Three-way translocation involving MLL, MLLT1, and a novel third partner, NRXN1, in a patient with acute lymphoblastic leukemia and t(2;19;11) (p12;p13.3;q23).
abstract: Translocations involving mixed lineage leukemia (MLL) gene at 11q23 are associated with de novo acute leukemia as well as therapy-related acute leukemia. More than 100 different translocations involving MLL have been described in acute leukemia, with more than 60 translocation partner genes characterized on the molecular level. In addition to various simple translocations affecting MLL, there are also complex forms involving three or more chromosomes. Here, we describe a novel three-way translocation of t(2;19;11)(p12;p13.3;q23) in a patient with acute lymphoblastic leukemia (ALL). In this translocation, the distal 19p13.3 joins the proximal 11q23 on der(11), whereas the distal 11q23 is translocated to 2p12. Three-way translocations involving 11q23 are often difficult to detect with cytogenetic means alone. In the present case, however, the chromosomes involved in the three-way translocation were readily identifiable by GTG banding. The MLL-MLLT1 fusion products from the derivative chromosome 11 were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), and two splicing variant forms were confirmed by cloning and sequencing. Furthermore, the novel third partner gene, NRXN1, was detected by systematic breakpoint analysis using long-distance inverse-PCR methods (LDI-PCR). The apparent three-way translocation thus identified is noteworthy because few studies have reported complex rearrangements involving 11q23 and 19p13.3 in acute leukemias.
authors.affiliation: Department of Laboratory Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul, Korea.
authors.forename: Sang-Guk
authors.initials: SG
authors.lastname: Lee
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Park
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Won
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Song
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Lee
authors.forename: Jong Rak
authors.initials: JR
authors.lastname: Choi
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
mesh_terms: D001483:Base Sequence; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D002889:Chromosomes, Human, Pair 2; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D009687:Nuclear Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C497422:KMT2A protein, human; C081448:MLLT1 protein, human; C539628:NRXN1 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D009687:Nuclear Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase