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

Abstract

Acute leukaemia in early childhood - and mainly infant leukaemia (IL)–ischaracterized by acquired genetic alterations, most commonly by the pres-ence of distinctMLLrearrangements (MLL-r). The aim of this study wasto investigate possible correlations between clinical features and molecularanalyses of a series of 545 childhood leukaemia ( 24 months of age)cases: 385 acute lymphoblastic leukaemia (ALL) and 160 acute myeloid leu-kaemia (AML). The location of the genomic breakpoints was determinedin a subset of 30MLL-rcases. The overall survival of the investigatedcohort was 60 5%, as determined by the Kaplan-Meier method. Worse out-comes were associated with age at diagnosis 6 months (P<0 001), highwhite blood cell count (P=0 001), andMLL-r (P=0 002) in ALL, whilechildren with AML displayed a poorer outcome (P=0 009) regardless oftheir age strata. Moreover, we present first evidence thatMLL-r patientswith poor outcome preferentially displayed chromosomal breakpointswithinMLLintron 11. Based on the literature, mostMLL-r IL display abreakpoint localization towards intron 11, which in turn may explain theirworse clinical course. In summary, theMLLbreakpoint localization is ofclinical importance and should be considered as a novel outcome predictorforMLL-r patients