The role of acute myeloid leukemia (AML) mutations in the pathogenesis of the disease has not been fully understood, and many genomic mutations in AML remain unknown. A team of researchers has recently analyzed large databases of genetic mutations and has selected 200 adult cases of de novo AML for their new study, using a variety of methods of genomic sequencing (The Cancer Genome Atlas Research Network. N Engl J Med. 2013 May 1. [Epub ahead of print]).
Results show that AML genes are associated with the fewest mutations of all types of adult cancers, with an average of only 13 mutations. Of these, 5 mutations on average are in genes that recur in AML in the various phenotypes. A total of 23 genes were significantly associated with AML mutations, and 237 genes were mutated in ≥2 samples. The majority of the samples had ≥1 nonsynonymous mutations in 1 of 9 gene types that are believed to be associated with the pathogenesis of AML; these include transcription-factor fusions, the gene encoding nucleophosmin (NPM1), tumor-suppressor genes, DNA-methylation–related genes, signaling genes, chromatin-modifying genes, myeloid transcription-factor genes, cohesin-complex genes, and spliceosome-complex genes. The classification of the mutated genes into 9 categories reveals strong biologic relationships that will likely have important clinical implications.
The team identified at least 1 potential driver mutation in nearly every sample of AML subtype that was investigated, indicating that the complex genetic interaction is linked to the pathogenesis of this malignancy in each patient. The large database will be used to further study the nature of AML and to develop new targeted therapies for this patient population.
