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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/44780

Title: Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms
Authors: Hernández Jerez, Antonio Francisco
Menéndez, Pablo
Issue Date: 2016
Abstract: Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events. View Full-Text
Sponsorship: Antonio F. Hernández research was partially supported by grants from the Council of Health (PI-0682-2013) and the Council of Innovation (P09-CVI-5062) of the Andalusian Government. Work in Pablo Mendéndez’s laboratory is supported by the European Research Council (ERC-2014-CoG-646903), the Spanish Ministry of Economy and Competitiveness (MINECO and Instituto de Salud Carlos III (ISCIII)/Fondo Europeo de Desarrollo regional (FEDER), the Foundation Inocente Inocente, the Spanish Association of Cancer Research, the Catalunya Government (SGR330) and Celgene. Pablo Menéndez also acknowledges financial support from The Obra Social La Caixa-Fundaciò Josep Carreras. Pablo Menéndez is an investigator of the Spanish Cell Therapy cooperative network (Red de Terapia Celular, TERCEL).
Publisher: MDPI
Keywords: Leukemia
Hematopoietic stem/progenitor cells
Chromosomal rearrangements
Topoisomerase II
DNA double-strand break
Oxidative stress
URI: http://hdl.handle.net/10481/44780
ISSN: 1422-0067
Citation: Hernández Jerez, A.F.; Menéndez, P. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms. International Journal of Molecular Sciences, 17(4): 461 (2016). [http://hdl.handle.net/10481/44780]
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