2024/01/11 by Masayuki Umeda, Jing Ma, Tamara Westover +22 · 4 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Acute Myeloid Leukemia Research #Cancer Genomics and Diagnostics #Epigenetics and DNA Methylation
paper · pdf · doi:10.1038/s41588-023-01640-3
openalex publication_date 2024/01/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Recent studies on pediatric acute myeloid leukemia (pAML) have revealed pediatric-specific driver alterations, many of which are underrepresented in the current classification schemas. To comprehensively define the genomic landscape of pAML, we systematically categorized 887 pAML into 23 mutually distinct molecular categories, including new major entities such as UBTF or BCL11B, covering 91.4% of the cohort. These molecular categories were associated with unique expression profiles and mutational patterns. For instance, molecular categories characterized by specific HOXA or HOXB expression signatures showed distinct mutation patterns of RAS pathway genes, FLT3 or WT1, suggesting shared biological mechanisms. We show that molecular categories were strongly associated with clinical outcomes using two independent cohorts, leading to the establishment of a new prognostic framework for pAML based on these updated molecular categories and minimal residual disease. Together, this comprehensive diagnostic and prognostic framework forms the basis for future classification of pAML and treatment strategies.