Genomic characterization of cancer has transformed understanding of the pathogenesis for all types of cancer in the last two decades, with the study of hematologic malignancies at the forefront of the genomics revolution. With continuous rapid advances, as we envision future possibilities in diagnosis, it is helpful to reflect upon how we reached this point. This review includes a historical perspective, and touches upon significant milestones since the microscope’s invention in 1674 toward the current diagnosis of acute myeloid leukemia (AML), which is an example of an aggressive hematologic malignancy that now requires integration with genomics for diagnosis, prognosis and clinical management. The 2016/2017 World Health Classification (WHO) classification criteria precisely identify AML with recurrent chromosomal abnormalities and the two new, molecularly-defined subtypes, AML with mutated NPM1 (AML-NPM1mut) and biallelic mutated CEBPA (AML-biCEBPAmut). Epidemiologic and hematologic features of the two new molecularly-defined WHO subtypes of AML are highlighted, including for familial AML-NPM1mut and familial AML-biCEBPAmut. Genomic testing, in conjunction with cytomorphologic evaluation, flow cytometric immunophenotypic, and cytogenetic analysis, is now essential for accurate diagnosis of AML. In light of current guidelines for testing, risk stratification, and newer therapies, considerations for integrated genomic testing are discussed toward routine diagnosis by the WHO classification of AML.
Diagnostic classification, Acute myeloid leukemia, Familial leukemia, Genomics, Smoking, Epidemiology, Mutations, Cytogenetics, Flow cytometry, World Health Organization