In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia.
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.
Wiemels
Joseph L
JL
Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, University of California San Francisco 94143-0560, USA. jwiemels@epi.ucsf.edu
Xiao
Zhijian
Z
Buffler
Patricia A
PA
Maia
Ana T
AT
Ma
Xiaomei
X
Dicks
Brian M
BM
Smith
Martyn T
MT
Zhang
Luoping
L
Feusner
James
J
Wiencke
John
J
Pritchard-Jones
Kathy
K
Kempski
Helena
H
Greaves
Mel
M
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
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