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The myeloid leukemias are a heterogeneous group of diseases characterized by infiltration of the blood, bone marrow, and other tissues by neoplastic cells of the hematopoietic system. In 2010 the estimated number of new myeloid leukemia cases in the United States was 17,200. These leukemias comprise a spectrum of malignancies that, untreated, range from rapidly fatal to slowly growing. Based on their untreated course, the myeloid leukemias have traditionally been designated acute or chronic.

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Incidence

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The incidence of acute myeloid leukemia (AML) is ∼3.5 per 100,000 people per year, and the age-adjusted incidence is higher in men than in women (4.3 vs 2.9). AML incidence increases with age; it is 1.7 in individuals aged <65 years and 15.9 in those aged >65 years. The median age at diagnosis is 67 years.

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Etiology

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Heredity, radiation, chemical and other occupational exposures, and drugs have been implicated in the development of AML. No direct evidence suggests a viral etiology.

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Heredity

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Certain syndromes with somatic cell chromosome aneuploidy, such as trisomy 21 noted in Down syndrome, are associated with an increased incidence of AML. Inherited diseases with defective DNA repair, e.g., Fanconi anemia, Bloom syndrome, and ataxia-telangiectasia, are also associated with AML. Congenital neutropenia (Kostmann syndrome) is a disease with mutations in the granulocyte colony-stimulating factor (G-CSF) receptor and, often, neutrophil elastase that may evolve into AML. Myeloproliferative syndromes may also evolve into AML (Chap. 108). Germ-line mutations of CCAAT/enhancer-binding protein α (CEBPA), runt-related transcription factor 1 (RUNX1), and tumor protein p53 (TP53) have also been associated with a higher predisposition to AML in some series.

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Radiation

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High-dose radiation, like that experienced by survivors of the atomic bombs in Japan or nuclear reactor accidents, increase the risk of myeloid leukemias that peak 5–7 years after exposure. Therapeutic radiation alone seems to add little risk of AML but can increase the risk in people also exposed to alkylating agents.

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Chemical and Other Exposures

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Exposure to benzene, a solvent used in the chemical, plastic, rubber, and pharmaceutical industries, is associated with an increased incidence of AML. Smoking and exposure to petroleum products, paint, embalming fluids, ethylene oxide, herbicides, and pesticides have also been associated with an increased risk of AML.

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Drugs

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Anticancer drugs are the leading cause of therapy-associated AML. Alkylating agent–associated leukemias occur on average 4–6 years after exposure, and affected individuals have aberrations in chromosomes 5 and 7. Topoisomerase II inhibitor–associated leukemias occur 1–3 years after exposure, and affected individuals often have aberrations involving chromosome 11q23. Chloramphenicol, phenylbutazone, and, less commonly, chloroquine and methoxypsoralen can result in bone marrow failure that may evolve into AML.

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Classification

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The current categorization of AML uses the World Health Organization (WHO) ...

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