The distribution of MLL breakpoints correlates with outcome in infant acute leukaemia

Acute leukaemia in early childhood - and mainly infant leukaemia (IL) is characterized by acquired genetic alterations, most commonly by the presence of distinct MLL rearrangements (MLL-r). The aim of this study was to investigate possible correlations between clinical features and molecular analyses of a series of 545 childhood leukaemia (24months of age) cases: 385 acute lymphoblastic leukaemia (ALL) and 160 acute myeloid leukaemia (AML). The location of the genomic breakpoints was determined in a subset of 30 MLL-r cases. The overall survival of the investigated cohort was 60 center dot 5%, as determined by the Kaplan-Meier method. Worse outcomes were associated with age at diagnosis 6months (P<0 center dot 001), high white blood cell count (P=0 center dot 001), and MLL-r (P=0 center dot 002) in ALL, while children with AML displayed a poorer outcome (P=0 center dot 009) regardless of their age strata. Moreover, we present first evidence that MLL-r patients with poor outcome preferentially displayed chromosomal breakpoints within MLL intron 11. Based on the literature, most MLL-r IL display a breakpoint localization towards intron 11, which in turn may explain their worse clinical course. In summary, the MLL breakpoint localization is of clinical importance and should be considered as a novel outcome predictor for MLL-r patients.