Acute myeloid leukemia (AML) is a heterogeneous disease with distinctive genetic abnormalities. The application of genetic and genomic technologies to identify recurrent abnormalities and the integration of these data with morphology, flow cytometry, immunohistochemistry and clinical findings provide a more comprehensive understanding of these disorders [[1], [2], [3]]. Genomic studies are indicated in multiple scenarios, including, at diagnosis, relapse, interval time points during remission, and pre- and post-bone marrow transplantation. In the diagnostic setting, genomic studies are essential to guide immediate management of the patient, including subclassification of the AML (e.g. NPM1-mutated AML, [1]) or determination of prognosis and risk stratification (e.g. TP53 mutations [3]). While the previous WHO edition (revised 4th edition [1]) included specific AML categories that could be defined without regard to the traditional cutoff (20 %) to blast percentage, the new WHO and ICC have redefined the blast cutoff criterion. In most situations, this allows AML diagnoses to weigh more heavily on discovered genomic alterations which would allow targeted treatment interventions to commence sooner. These changes are discussed later in this paper, to compare and contrast the commonalities and differences between the ICC [3] and WHO [2] classification definitions and diagnostic criteria in AML.

Multiple techniques are used to detect cytogenetic and genomic abnormalities in AML. For cytogenetics studies, these include chromosome analysis (karyotyping), Fluorescence in Situ Hybridization (FISH), Chromosomal Microarrays (CMA), and Optical Genome Mapping (OGM). For molecular techniques, these include but are not limited to Sanger Sequencing, various PCR based assays and Next Generation Sequencing (NGS)/Massively Parallel Sequencing (MPS) [4]. Each of these methodologies for detection of genomic abnormalities has advantages and limitations, and continue to evolve [5]. This review will focus on recurrent cytogenetic and genomic abnormalities detected in AML, the evolving landscape of genomics in these disorders, the incorporation of these results into pathologic diagnosis and clinical decision-making and advancing technologies to facilitate improvements in broad genomic profiling.

Recently, both the World Health Organization (WHO) [2] and the International Consensus Classification (ICC) [3] have incorporated additional genomic changes into the classification schemes of AML, which include cytogenetic and molecular findings. In addition to the expansion of genetic abnormalities into the classification of AML, both the WHO and ICC have modified the blast percentage cutoff for most AML categories, with notable differences between the two classification systems. The WHO decided to eliminate the 20 % blast requirement for all AML types with defining genetic aberrations, with exceptions that include AML with BCR::ABL1 fusion and AML with CEBPA mutation. AML, myelodysplasia-related, however, requires a 20 % blast cutoff together with specific cytogenetic and gene abnormalities associated with myelodysplastic syndrome (MDS). Conversely, the ICC has chosen to reduce the blast cutoff assignment to 10 % for nearly all AML types, except for AML with t (9; 22) (34.1; q11.2)/BCR::ABL. Moreover, for myeloid neoplasms that demonstrate MDS characterization or exhibit myelodysplasia-related cytogenetic abnormalities/gene mutations (later discussed), with 10–19 % blasts, these must be labeled with the qualifier of MDS/AML. Some other notable differences include the ICC's removal of the prior standalone categories of therapy-related myeloid neoplasms and AML with myelodysplasia-related changes [Arber 2022]. The WHO arranged AML diagnosis into three families: AML with defining genetic abnormalities, AML defined by differentiation, and myeloid sarcoma. The continued detection and annotation of genetic aberrations in AML has led to remarkable progress in understanding the molecular pathogenesis and development of targeted therapies [6].

Risk classification of AML has historically been driven by the detection of cytogenetic abnormalities and molecular alterations; however, the most recent European Leukemia Net (ELN) includes both the diagnostic abnormalities for risk classification and the ability to reclassify a patient based on the presence or absence of MRD [7].