Chromosomal and Genomic Alterations in Pediatric AML

The configuration of specific chromosomal and genomic alterations has increasingly formed the basis for pediatric acute myeloid leukemia (AML) diagnosis and prognostication. Clinically significant alterations most often come in the form of fusion oncogenes, chromosome losses, and cancer gene mutations (e.g., single nucleotide variants, insertions/deletions, and internal tandem duplications). Genes that encode transcription factors and signal transduction pathway proteins are most frequently altered, with the former most often disrupting normal hematopoiesis and the latter contributing to aberrant survival and growth. Recent large-scale sequencing efforts have significantly expanded the number of clinically important and previously cryptic genomic alterations, while also laying the foundation for hypothesis-driven research leading to ongoing advances in fields of research that include but are not limited to leukemogenesis, clinical risk stratification, molecular therapeutics, and residual disease detection.