Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms

摘要: Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation survival differentiation-blocked clone. Pediatric leukemia phenotypically genetically heterogeneous with an obscure etiology. interaction between factors environmental agents represents a potential etiological driver. Although information limited, principal toxic mechanisms leukemogenic (e.g., etoposide, benzene metabolites, bioflavonoids some pesticides) include topoisomerase II inhibition excessive generation free radicals, which may induce DNA single- double-strand breaks (DNA-DSBs) early HSPCs. Chromosomal rearrangements (duplications, deletions translocations) occur if these lesions are not properly repaired. initiating hit usually occurs utero commonly leads to expression oncogenic fusion proteins. Subsequent cooperating hits define latency after birth be genetic, epigenetic or immune nature (i.e., delayed infection-mediated deregulation). Here, we review available experimental epidemiological evidence linking pesticide exposure infant provide mechanistic basis support association, focusing on molecular events.