Meyer, C2; Hofmann, Julian3; Burmeister, T4; Gröger, D4; Park, T S4; Emerenciano, M4; Pombo de Oliveira, M4; Renneville, A4; Villarese, P4; Macintyre, E4; Cavé, H4; Clappier, E4; Mass-Malo, K4; Zuna, J4; Trka, J4; De Braekeleer, E4; De Braekeleer, M4; Oh, S H4; Tsaur, G4; Fechina, L4; van der Velden, V H J4; van Dongen, J J M4; Delabesse, E4; Binato, R4; Silva, Maria5; Kustanovich, A4; Aleinikova, O4; Harris, M H4; Lund-Aho, T4; Juvonen, V4; Heidenreich, O4; Vormoor, J4; Choi, W W L4; Jarosova, M4; Kolenova, A4; Bueno, C4; Menendez, P4; Wehner, Stine Kjær6; Eckert, C4; Talmant, P4; Tondeur, S4; Lippert, Eva7; Launay, E4; Henry, C4; Ballerini, P4; Lapillone, H4; Callanan, M B4; Cayuela, J M4; Herbaux, C4; Cazzaniga, G4; Kakadiya, P M4; Bohlander, S4; Ahlmann, M4; Choi, Jeong-Heon8; Gameiro, P4; Lee, D S4; Krauter, J4; Cornillet-Lefebvre, P4; Te Kronnie, G4; Schäfer, B W4; Kubetzko, S4; Alonso, C N4; zur Stadt, U4; Sutton, R4; Venn, N C4; Izraeli, S4; Trakhtenbrot, L4; Madsen, H O1; Archer, P4; Hancock, J4; Cerveira, N4; Teixeira, M R4; Lo Nigro, L4; Möricke, A4; Stanulla, M4; Schrappe, M4; Sedék, L4; Szczepański, T4; Zwaan, C M4; Coenen, E A4; van den Heuvel-Eibrink, M M4; Strehl, S4; Dworzak, M4; Panzer-Grümayer, R4; Dingermann, T4; Klingebiel, T4; Marschalek, R4
1 Klinisk Immunologisk Afdeling. Blodbanken og Vævstypelaboratoriet, Diagnostisk Center, Rigshospitalet, The Capital Region of Denmark2 Department of Biochemistry, Chemistry and Pharmacy, Institute of Pharmaceutical Biology/ZAFES/Diagnostic Center of Acute Leukemia (DCAL), Goethe-University of Frankfurt, Frankfurt/Main, Germany.3 Institut for Miljø- og Erhvervsøkonomi4 unknown5 Sektionen for Geoinformatik og Arealforvaltning6 Krop, læring og identitet7 JUR Juridisk Bacheloruddannelse8 Risø National Laboratory for Sustainable Energy
Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (≈ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.
Leukemia, 2013, Vol 27, Issue 11, p. 2165-76
Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't