Abstract
Derivative chromosomes of 40 patients diagnosed with t(4;11) acute lymphoblastic leukemia (ALL) were analysed on the genomic DNA level. Chromosomal breakpoints were identified in most cases within the known breakpoint cluster regions of the involved MLL and AF4 genes. Due to our current knowledge of the primary DNA sequences of both breakpoint cluster regions, specific features were identified at the chromosomal fusion sites, including deletions, inversions and duplications of parental DNA sequences. After separation of all t(4;11) leukemia patients into two age classes (below and above 1 year of age), the analysis of chromosomal fusion sites revealed significant differences in the distribution of chromosomal breakpoints and led to the definition of two hotspot areas within the MLL breakpoint cluster region. This may point to the possibility of different age-linked mechanisms that were leading to t(4;11) chromosomal translocations.
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Acknowledgements
We are grateful to all physicians who provided DNA from biopsy material of t(4;11) leukemia patients, especially Drs F Cotter (London, UK), B Emmerich (Munich, Germany), M Gramatzki (Erlangen, Germany), and U zur Stadt (Hamburg; Germany). This study was supported by research grants SFB 466 from the Deutsche Forschungsgemeinschaft (DFG) to J Greil and R Marschalek, research grant 96.047.3 from the Wilhelm Sander Foundation to GH Fey, J Greil and R Marschalek, and NCI grant CA-13539 to FM Uckun. FM Uckun is a Stohlman Scholar of the Leukemia Society of America.
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Reichel, M., Gillert, E., Angermüller, S. et al. Biased distribution of chromosomal breakpoints involving the MLL gene in infants versus children and adults with t(4;11) ALL. Oncogene 20, 2900–2907 (2001). https://doi.org/10.1038/sj.onc.1204401
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DOI: https://doi.org/10.1038/sj.onc.1204401
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