Klin Padiatr 2009; 221 - A27
DOI: 10.1055/s-0029-1222648

Bimodal distribution of genomic MLL breakpoints in infant acute lymphoblastic leukemia

R Jung 1, U Jacobs 1, S Semper 1, T Langer 1, A Moericke 2, M Stanulla 2, M Schrappe 2, M Metzler 1
  • 1Department of Pediatrics, University of Erlangen-Nuremberg, Erlangen, Germany
  • 2Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

Background: A hallmark of infant leukemia is the high prevalence of chromosomal rearrangements involving the MLL gene. The most frequent partner genes are AF4, AF9, and ENL. Aim of this study was to assess breakpoint distribution within the MLL gene to evaluate association of recombination related sequence DNA motifs.

Patients/Methods: The genomic fusion sites from 59 infant MLL samples (33 MLL-AF4, 10 MLL-AF9 and 16 MLL-ENL) were analyzed. Kernel density analysis and scan statistics were used to describe breakpoint distribution and clustering.

Results: In contrast to previous studies based on smaller cohorts, breakpoints in proximity to the telomeric topo II cleavage site represent only a fraction of infant MLL cases. The total group as well as the MLL-AF4, MLL-AF9 and MLL-ENL subgroups, showed a bimodal breakpoint distribution compatible with a combination of topo II and scaffold attachment region associated DNA breakage followed by homologous end joining repair.

Conclusion: We therefore suggest that at least two different mechanisms are relevant in infant MLL translocation initiation.