Produção Nacional
Revisado por pares
The MLL recombinome of acute leukemias in 2017
2017; Springer Nature; Volume: 32; Issue: 2 Linguagem: Inglês
10.1038/leu.2017.213
ISSN1476-5551
AutoresClaus Meyer, Thomas Burmeister, Daniela Gröger, Grigory Tsaur, Л. Г. Фечина, Aline Renneville, Rosemary Sutton, Nicola C. Venn, Mariana Emerenciano, Maria S. Pombo‐de‐Oliveira, Caroline Barbieri Blunck, Bruno A. Lopes, Jan Zuna, Jan Trka, Paola Ballerini, Hélène Lapillonne, Marc De Braekeleer, Giovanni Cazzaniga, L Corral Abascal, Vincent H. J. van der Velden, Éric Delabesse, T S Park, Seung Hwan Oh, Maria Luiza Macedo Silva, T Lund-Aho, Vesa Juvonen, Andrew S. Moore, Olaf Heidenreich, Josef Vormoor, Elena Zerkalenkova, Yulia Olshanskaya, Clara Bueno, Pablo Menéndez, Andrea Teigler‐Schlegel, Udo zur Stadt, Jana Lentes, Gudrun Göhring, Anatoly Kustanovich, Olga Aleinikova, Beat W. Schäfer, Susanne Kubetzko, H O Madsen, Bernd Gruhn, Ximo Duarte, Paula Gameiro, Éric Lippert, Audrey Bidet, J M Cayuela, Emmanuelle Clappier, Cristina N. Alonso, C. Michel Zwaan, Marry M. van den Heuvel‐Eibrink, Shai Izraeli, L. Trakhtenbrot, Paul A. Archer, Jerry Hancock, Anja Möricke, Julia Alten, Martin Schrappe, Martin Stanulla, Sabine Strehl, Andishe Attarbaschi, Michael Dworzak, Oskar A. Haas, R Panzer-Grümayer, Łukasz Sędek, Tomasz Szczepański, Aurélie Caye, Lydia Suarez, Hélène Cavé, Rolf Marschalek,
Tópico(s)Epigenetics and DNA Methylation
ResumoChromosomal 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.
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