The MLL recombinome of acute leukemias in 2013

  • 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.

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Author:Claus Meyer, J Hofmann, T Burmeister, D Gröger, TS Park, M Emerenciano, M Pombo de Oliveira, A Renneville, E Macintyre, H Cavé, E Clappier, K Mass-Malo, J Zuna, J Trka, E De Braekeleer, M De Braekeleer, SH Oh, G Tsaur, L Fechina, VH van der Velden, JJ van Dongen, E Delabesse, R Binato, ML Silva, A Kustanovich, O Aleinikova, MH Harris, T Lund-Aho, V Juvonen, O Heidenreich, J Vormoor, WW Choi, M Jarosova, A Kolenova, C Bueno, P Menendez, S Wehner, C Eckert, P Talmant, S Tondeur, E Lippert, E Launay, C Henry, P Ballerini, H Lapillone, MB Callanan, JM Cayuela, C Herbaux, G Cazzaniga, PM Kakadiya, Stefan Klaus Bohlander, M Ahlmann, JR Choi, P Gameiro, DS Lee, J Krauter, P Cornillet-Lefebvre, G Te Kronnie, BW Schäfer, S Kubetzko, CN Alonso, U zur Stadt, R Sutton, NC Venn, S Izraeli, L Trakhtenbrot, HO Madsen, P Archer, J Hancock, N Cerveira, MR Teixeira, L Lo Nigro, A Möricke, M Stanulla, M Schrappe, L Sedék, T Szczepański, CM Zwaan, EA Coenen, MM van den Heuvel-Eibrink, S Strehl, Michael N. Dworzak, Renate Panzer-Grümayer, Theodor DingermannORCiDGND, Thomas KlingebielORCiDGND, Rolf MarschalekORCiDGND
URN:urn:nbn:de:hebis:30:3-355505
DOI:https://doi.org/10.1038/leu.2013.135
ISSN:1476-5551
ISSN:0887-6924
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/23628958
Parent Title (English):Leukemia
Publisher:Nature Publ. Group
Place of publication:Basingstoke
Document Type:Article
Language:English
Date of Publication (online):2013/05/17
Date of first Publication:2013/05/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/11/22
Tag:ALL; AML; MLL; acute leukemia; chromosomal translocations; translocation partner genes
Volume:27
Issue:11
Page Number:12
First Page:2165
Last Page:2176
Note:
Copyright © 2013 Macmillan Publishers Limited This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
HeBIS-PPN:36686288X
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0