key papersKey paper
The molecular landscape of paediatric acute myeloid leukaemia (TARGET)
Sequencing nearly a thousand childhood acute myeloid leukaemias showed the disease differs sharply from adult disease, with fewer mutations, more structural rearrangements and age-specific drivers, so adult genetic risk groups cannot simply be transferred to children.
Overview
Comprehensive genomic study by the TARGET initiative of 993 children and young adults with AML, including whole-genome, exome, transcriptome and methylation profiling, identifying age-specific patterns of somatic mutations, structural variants such as KMT2A and NUP98 rearrangements, and novel focal deletions.
Translational studyChanged practice993 participants
Findings
- Low mutation burden in childhood AML with structural variants and fusions predominating.
- Distinct age-associated mutations, for example NPM1 and DNMT3A being rare in young children.
What it means
Paediatric AML risk classification and targeted therapy development now rest on this landscape rather than on adult data.
Caveats
- Discovery cohort; clinical translation into risk stratification is ongoing.