Genetic abnormalities or the stage at which differentiation was halted form part of modern classification systems.Specific cytogenetic abnormalities can be found in many people with AML; the types of chromosomal abnormalities often have prognostic significance. The chromosomal translocations encode abnormal fusion proteins, usually transcription factors whose altered properties may cause the "differentiation arrest". For example, in APL, the t(15;17) translocation produces a PML-RARA fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid-specific genes and inhibits myeloid differentiation.The clinical signs and symptoms of AML result from the growth of leukemic clone cells, which tends to interfere with the development of normal blood cells in the bone marrow. This leads to neutropenia, anemia, and thrombocytopenia. Other symptoms can arise from the infiltration of malignant cells into parts of the body, such as the gingiva and skin.Many cells develop mutations in genes that affect epigenetics, such as DNA methylation. When these mutations occur, it is likely in the early stages of AML. Such mutations include in the DNA demethylase TET2 and the metabolic enzymes IDH1 and IDH2, which lead to the generation of a novel oncometabolite, D-2-hydroxyglutarate, which inhibits the activity of epigenetic enzymes such as TET2. Epigenetic mutations may lead to the silencing of tumor suppressor genes and/or the activation of proto-oncogenes. Diagnosis
A complete blood count, which is a blood test, is one of the initial steps in the diagnosis of AML.
The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiated monoblastic leukemia from ALL.The standard classification scheme for AML is the World Health Organization (WHO) system. According to the WHO criteria, the diagnosis of AML is established by demonstrating involvement of more than 20% of the blood and/or bone marrow by leukemic myeloblasts, except  in three forms of acute myeloid leukemia with recurrent genetic abnormalities: t(8;21), inv(16) or t(16;16), and acute promyelocytic leukemia with PML-RARA, in which the presence of the genetic abnormality is diagnostic irrespective of blast percent. Myeloid sarcoma is also considered a subtype of AML independently of the blast count. The older French-American-British (FAB) classification, which is no longer widely used, is a bit more stringent, requiring a blast percentage of at least 30% in bone marrow or peripheral blood for the diagnosis of AML.Because acute promyelocytic leukemia has the highest curability and requires a unique form of treatment, it is important to quickly establish or exclude the diagnosis of this subtype of leukemia. Fluorescent in situ hybridization performed on blood or bone marrow is often used for this purpose, as it readily identifies the chromosomal translocation [t(15;17)(q22;q12);] that characterizes APL. There is also a need to molecularly detect the presence of PML/RARA fusion protein, which is an oncogenic product of that translocation. World Health Organization
The WHO classification of AML attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria.