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Acute Leukemias

The MLL recombinome of acute leukemias

Abstract

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.

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Acknowledgements

This work was made possible by and conducted within the framework of the International BFM Study Group. We thank Reinald Repp, Thorsten Langer, Jörn-D Beck, Markus Metzler und Thomas Leis for providing and sharing unpublished information of their ongoing study (Grant 2002.032.1 from the Wilhelm Sander Foundation) and Michael Karas for critical comments. This study is supported by Grant GEN-AU Child, GZ 200.071/3-VI/2a/2002 to OAH and Grant 2001.061.1 from the Wilhelm-Sander-Foundation to RM, TD and TK.

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Correspondence to R Marschalek.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Meyer, C., Schneider, B., Jakob, S. et al. The MLL recombinome of acute leukemias. Leukemia 20, 777–784 (2006). https://doi.org/10.1038/sj.leu.2404150

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