Cytogenetic/molecular features of AML

Genetic analysis of leukemia blast cells (using both conventional cytogenetic methods and molecular methods) is performed on children with AML because both chromosomal and molecular abnormalities are important diagnostic and prognostic markers.[209-213] Clonal chromosomal abnormalities are identified in the blasts of about 75% of children with AML and are useful in defining subtypes with both prognostic and therapeutic significance. Detection of molecular abnormalities can also aid in risk stratification and treatment allocation. For example, variants of NPM and CEBPA are associated with favorable outcomes, while certain variants of FLT3 portend a high risk of relapse. Identifying the latter variants may allow for targeted therapy.[214-217]

Comprehensive molecular profiling of pediatric and adult AML has shown that AML is a disease demonstrating both commonalities and differences across the age spectrum.[218,219]

The 5th edition (2022) of the World Health Organization (WHO) Classification of Hematolymphoid Tumors, as well as the Inaugural WHO Classification of Pediatric Tumors, emphasize a multilayered approach to AML classification. These classifications consider multiple clinico-pathological parameters and seek a genetic basis for disease classification wherever possible.[222,223] These karyotypic abnormalities and other genomic alterations are used to define specific pediatric AML entities and are outlined in Table 3.[222,223]

In addition to the cytogenetic/molecular abnormalities that aid AML diagnosis, as defined by the WHO, there are additional entities that, while not disease-defining, have prognostic significance in pediatric AML. All prognostic abnormalities, both those defined by the WHO and these additional abnormalities, have been clustered according to favorable or unfavorable prognosis, as defined by contemporary Children's Oncology Group (COG) clinical trials. These entities are summarized below. After these entities are described, information about additional cytogenetic/molecular and phenotypic features associated with pediatric AML will be described. However, these additional features may not, at present, be used to aid in risk stratification and treatment.

While the t(15;17) fusion that results in the PML::RARA gene product is defined as a pediatric AML risk-defining lesion, given its association with acute promyelocytic leukemia, it is discussed in Childhood Acute Promyelocytic Leukemia.

Specific recurring cytogenetic and molecular abnormalities are briefly described below. The abnormalities are listed by those in clinical use that identify patients with favorable or unfavorable prognosis, followed by other abnormalities. The nomenclature of the 5th edition of the WHO classification is incorporated for disease entities where relevant.