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Home > Publications > Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia, 2013

Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia

NEJM 368:2059-2074 [doi:10.1056/NEJMoa1301689]


Many of the mutations that contribute to AML pathogenesis are still undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear.

We analyzed the genomes of 200 clinically-annotated cases of de novo acute myeloid leukemia occurring in adults, using whole genome sequencing (50 cases) or whole exome sequencing (150 cases), mRNA and miRNA sequencing, and DNA methylation analysis.

AML genomes are minimally mutated compared to other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples (99.5%) had at least one non-synonymous mutation in one of 9 categories of genes/events that are almost certainly relevant for pathogenesis, including transcription factor fusions (18% of cases), NPM1 (27%), tumor-suppressor genes (15.5%), DNA methylation-related genes (43.5%), signaling genes (59%), chromatin-modifying genes (30.5%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (13.5%).Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories.

Comprehensive genomic analyses have allowed us to identify at least one potential driver mutation in nearly all AML patients, and have revealed that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study will serve as a foundation for the understanding of AML pathogenesis, classification, and risk stratification.

Associated Data Files

These data represent a data freeze from January 8, 2013. Please note that more recent data are available via the TCGA Data Portal.

The data are supported by different organizations. All data marked by [DCC] are DCC-validated archives. All data marked by [Supplementary] were created by the manuscript authors and you should contact the corresponding author for support.

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Complete LAML Sample List


RNA Expression

SNP and Copy Number




Supplemental Data from NEJM paper [Supplementary]

Additional Information