title: In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia.
abstract: Recent reports have established the prenatal origin of leukemia translocations and resultant fusion genes in some patients, including MLL-AF4 translocations in infants and TEL-AML1 translocations in children. We now report evidence for the prenatal origin of a translocation in childhood acute myeloid leukemia (AML). The t(8;21) AML1-ETO translocations were sequenced at the genomic level in 10 diagnostic leukemia samples from children with available neonatal Guthrie blood spots. Clonotypic genomic AML1-ETO sequences were detected in the Guthrie spots for 5 individuals, providing unambiguous evidence of prenatal origin in these cases. Two of these patients were older than 10 years of age at diagnosis, indicative of a protracted postnatal latency. Three of the patients were assessed for the persistence of genomic fusion sequences in complete clinical remission samples and were found to be positive. These data indicate that t(8;21) in childhood AML can arise in utero, possibly as an initiating event in childhood AML, and may establish a long-lived or stable parental clone that requires additional secondary genetic alterations to cause leukemia.
authors: Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, University of California San Francisco 94143-0560, USA. jwiemels@epi.ucsf.edu
authors: Joseph L
authors: JL
authors: Wiemels
authors: Zhijian
authors: Z
authors: Xiao
authors: Patricia A
authors: PA
authors: Buffler
authors: Ana T
authors: AT
authors: Maia
authors: Xiaomei
authors: X
authors: Ma
authors: Brian M
authors: BM
authors: Dicks
authors: Martyn T
authors: MT
authors: Smith
authors: Luoping
authors: L
authors: Zhang
authors: James
authors: J
authors: Feusner
authors: John
authors: J
authors: Wiencke
authors: Kathy
authors: K
authors: Pritchard-Jones
authors: Helena
authors: H
authors: Kempski
authors: Mel
authors: M
authors: Greaves
mesh_terms: D000208:Acute Disease; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D012074:Remission Induction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors