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Abstract

Title: Causative agents in the etiology of Myelodysplastic Syndromes and the acute Myeloid Leukemias.
Author: Smith MT, Linet MS, Morgan GJ
Journal: In: The myelodysplastic syndromes: pathobiology and clinical management (Bennet JM (ed ) New York: Marcel Dekker :29-63
Year: 2002
Month: None

Abstract: [Myeloid malignancies and related disorders orginate in pluripotential precursor cells that normally give rise to red blood cells, polymorphonuclear neutrophils, monocytes, and platelets. Disruptions of the normal hierarchy of myeloid maturation result in hematological disorders characterized by either excess or deficienties of the mature effector cells. The disorders of myeloid origin include acute myeloid leukemia (AML, in which myeloid stem cell matureation is blocked by genetic changes, subsequently resulting in transformation to AML), myelodysplastic syndromes (MDS, in which disordered but relatively complete maturation occurs), and the myeloproliferative disorders such as chronic myeloid leukemia (CML, in which disordered but complete maturation occurs, followed after 3-4 years by blast crisis and transformation to AML). AML may arise de novo or following a myelodysplastic or myeloproliferative state. De novo and secondary AML are morphologically similar in appearance, but specific cytogenetic abnormalities are associated with secondary AML occurring after use of certain categories of chemotherapy drugs. A wide variety of exposures have been linked with increased risk of MDS and AML, including ionizing radiation, radiation therapy for malignant and benign conditions, occupational sources of radiation exposure, numerous chemotherapeutic agents (including alkylating agents, topoisomerase II inhibitors, and others), benzene, other chemicals (e.g. 2,3,7,8 tetrachlorobibenzo-p-dioxin, 1,3-butadiene, various solvents), agriculture exposures (suspected agents include pesticides, fertilizers, diesel fuel and exhaust, unknown infectious agents), cigarette smoking, hair dyes (particularly darkening agents), viruses (possivly HHV-6) and perhaps dietary factors (including potentially phenol and hydroquinone occurring in foods and beverages or from metabolic activity of intestinal bacterial microflora). Despite the wide variety of postulated exposures, the causes of the majority of cases of AML and MDS within the population are unknown.].