The MLL recombinome of acute leukemias in 2017 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-02

AUTHORS

C Meyer, T Burmeister, D Gröger, G Tsaur, L Fechina, A Renneville, R Sutton, N C Venn, M Emerenciano, M S Pombo-de-Oliveira, C Barbieri Blunck, B Almeida Lopes, J Zuna, J Trka, P Ballerini, H Lapillonne, M De Braekeleer, G Cazzaniga, L Corral Abascal, V H J van der Velden, E Delabesse, T S Park, S H Oh, M L M Silva, T Lund-Aho, V Juvonen, A S Moore, O Heidenreich, J Vormoor, E Zerkalenkova, Y Olshanskaya, C Bueno, P Menendez, A Teigler-Schlegel, U zur Stadt, J Lentes, G Göhring, A Kustanovich, O Aleinikova, B W Schäfer, S Kubetzko, H O Madsen, B Gruhn, X Duarte, P Gameiro, E Lippert, A Bidet, J M Cayuela, E Clappier, C N Alonso, C M Zwaan, M M van den Heuvel-Eibrink, S Izraeli, L Trakhtenbrot, P Archer, J Hancock, A Möricke, J Alten, M Schrappe, M Stanulla, S Strehl, A Attarbaschi, M Dworzak, O A Haas, R Panzer-Grümayer, L Sedék, T Szczepański, A Caye, L Suarez, H Cavé, R Marschalek

ABSTRACT

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients. More... »

PAGES

273

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/leu.2017.213

    DOI

    http://dx.doi.org/10.1038/leu.2017.213

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1090671685

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28701730


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