Diagnosis and Classification of AML: WHO 2016

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by intrinsic genetic complexity, present at diagnosis and/or evolving during the disease course. Due to the significant prognostic role of genetic changes in AML, characterization of molecular and phenotypic profiles is essential to designing patient- and disease-specific strategies aimed at preventing disease relapse and improving long-term outcome. In recent years, deep biological knowledge emerging in myeloid neoplasms led to the revised edition of the World Health Organization (WHO) classification in 2016. Accordingly, the rules for AML classification require collection of the patient’s history, including previous cytotoxic therapies, which define “therapy-related myeloid neoplasms,” or a prior history of MDS or MPN, defining “AML with myelodysplasia-related changes” (“AML-MRC”). The second field of investigation for classifying a case of AML is the presence of specific gene mutations or rearrangements defining the category of “AML with recurrent genetic abnormalities”. The detection of balanced or unbalanced cytogenetics aberrations considered associated with MDS and/or detection of multilineage dysplasia by morphology, defines the disease as “AML-MRC.” When the disease cannot be classified in another category, the morphologic exam of bone marrow and peripheral blood is the only parameter useful in the subcategorization of “AML, not otherwise specified" ("AML-NOS"). Recently, high-throughput next-generation techniques have indeed showed the accumulation of multiple genetic abnormalities in leukemic blasts. Not only do somatic mutations affect disease pathogenesis as single events, but also their combination plays a significant role. In this line, the European Leukemia Net (ELN) defined the first genetic-based stratification system for AML in 2010, and published a revised version in 2017. Three prognostic subgroups have been identified (favorable, intermediate, and adverse), where in addition to karyotype assessment, NPM1 mutation and evaluation of FLT3-ITD allelic burden, together with assessment of TP53, RUNX1, and ASXL1 mutations, are mandatory for proper AML stratification. In this chapter, we will also review the integrated diagnostic algorithm for AML diagnosis, nowadays an important challenge in the context of precision medicine, mandatory for the design of targeted-treatment approaches.