Historically, survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of AML, as did radiologists exposed to high levels of X-rays prior to the adoption of modern radiation safety practices. Genetics
Most cases of AML arise spontaneously, however there are some genetic mutations associated with an increased risk. Several congenital conditions increase the risk of leukemia; the most common is Down syndrome, with other more rare conditions including Fanconi anemia, Bloom syndrome and ataxia-telangiectasia (all characterised by problems with DNA repair), and Kostmann syndrome. Other factors
Being overweight and obese increase the risk of developing AML, as does any amount of active smoking. For reasons that may relate to substance or radiation exposure, certain occupations have a higher rate of AML; particularly work in the nuclear power industry, electronics or computer manufacturing, fishing and animal slaughtering and processing. Pathophysiology
The malignant cell in AML is the myeloblast. In normal development of blood cells (hematopoiesis), the myeloblast is an immature precursor of myeloid white blood cells; a normal myeloblast will mature into a white blood cell such as an eosinophil, basophil, neutrophil or monocyte. In AML, though, a single myeloblast accumulates genetic changes which stop maturation, increase its proliferation, and protect it from programmed cell death (apoptosis). Much of the diversity and heterogeneity of AML is because leukemic transformation can occur at a number of different steps along the differentiation pathway.
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.