The MLL recombinome of acute leukemias

C Meyer, B Schneider, S Jakob, S Strehl, A Attarbaschi, S Schnittger, C Schoch, M W J C Jansen, J J M van Dongen, M L den Boer, R Pieters, M-G Ennas, E Angelucci, U Koehl, J Greil, F Griesinger, U Zur Stadt, C Eckert, T Szczepański, F K NiggliB W Schäfer, H Kempski, H J M Brady, J Zuna, J Trka, L L Nigro, A Biondi, E Delabesse, E Macintyre, M Stanulla, M Schrappe, O A Haas, T Burmeister, T Dingermann, T Klingebiel, R Marschalek

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

171 Citaten (Scopus)

Samenvatting

Chromosomal rearrangements of the human MLL gene are a hallmark for aggressive (high-risk) pediatric, adult and therapy-associated acute leukemias. These patients need to be identified in order to subject these patients to appropriate therapy regimen. A recently developed long-distance inverse PCR method was applied to genomic DNA isolated from individual acute leukemia patients in order to identify chromosomal rearrangements of the human MLL gene. We present data of the molecular characterization of 414 samples obtained from 272 pediatric and 142 adult leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) was determined and several new TPGs were identified. The combined data of our study and published data revealed a total of 87 different MLL rearrangements of which 51 TPGs are now characterized at the molecular level. Interestingly, the four most frequently found TPGs (AF4, AF9, ENL and AF10) encode nuclear proteins that are part of a protein network involved in histone H3K79 methylation. Thus, translocations of the MLL gene, by itself coding for a histone H3K4 methyltransferase, are presumably not randomly chosen, rather functionally selected.

Originele taal-2Engels
Pagina's (van-tot)777-84
Aantal pagina's8
TijdschriftLeukemia
Volume20
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - mei 2006
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'The MLL recombinome of acute leukemias'. Samen vormen ze een unieke vingerafdruk.

Citeer dit