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INTRODUCTION

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SUMMARY

Acute myelogenous leukemia (AML) is the result of a sequence of somatic mutations in a primitive multipotential hematopoietic cell. Exposure to radiation, chronic exposure to high doses of benzene, and chronic inhalation of tobacco smoke increase the incidence of the disease. Obesity has been found to be an endogenous risk factor. A small but increasing proportion of cases develop after a patient with lymphoma, a nonhematologic cancer, or an autoimmune disorder is exposed to intensive chemotherapy, especially with alkylating agents or topoisomerase II inhibitors. The mutant (leukemic) hematopoietic cell acquires the features of a leukemic stem cell capable of self-renewal and desultory differentiation and maturation. It gains a growth and survival advantage in relationship to the normal polyclonal pool of hematopoietic stem cells. As the progeny of this mutant, now leukemic, multipotential cell proliferates to form approximately 10 to 100 billion or more cells, normal hematopoiesis is inhibited, and normal red cell, neutrophil, and platelet blood levels fall. The resultant anemia leads to weakness, exertional limitations, and pallor; the thrombocytopenia to spontaneous hemorrhage, usually in the skin and mucous membranes; and the neutropenia and monocytopenia to poor wound healing and minor infections. Severe infection usually does not occur at diagnosis, but often does if the disease progresses because of lack of treatment or if chemotherapy intensifies the decrease of blood neutrophil and monocyte levels. The diagnosis is made by measurement of blood cell counts and examination of blood and marrow cells and is based on identification of leukemic blast cells in the blood and marrow. The diagnosis of the myelogenous form of acute leukemia is confirmed specifically by identification of myeloperoxidase activity in blast cells or by identifying characteristic cluster of differentiation (CD) antigens on the blast cells (e.g., CD13, CD33). Because the leukemic stem cell is capable of imperfect differentiation and maturation, the clone may contain cells that have the morphologic or immunophenotypic features of erythroblasts, megakaryocytes, monocytes, eosinophils, or, rarely, basophils or mast cells, in addition to myeloblasts or promyelocytes. When one cell line is sufficiently dominant, the leukemia may be referred to by that lineage: for example, acute erythroid, acute megakaryocytic, acute monocytic leukemia, and so on. Certain cytogenetic alterations are more frequent; these abnormalities include t(8;21), t(15;17), inversion 16 or t(16;16), trisomy 8, and deletions of all or part of chromosome 5 or 7. A translocation involving chromosome 17 at the site of the retinoic acid receptor–α (RAR-α) gene is uniquely associated with acute promyelocytic leukemia. AML usually is treated with cytarabine and an anthracycline antibiotic, although other drugs may be added or substituted in poor-prognosis, older, refractory, or relapsed patients. The exception to this approach is the treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and sometimes an anthracycline antibiotic. High-dose chemotherapy and either autologous stem cell infusion or allogeneic hematopoietic stem cell transplantation may be used in an effort to treat relapse or patients at high risk to ...

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