Authors: Eiichi Ishii Mariko Eguchi Minenori EguchiIshimae Nobuyuki Yoshida Megumi Oda Masafumi Zaitsu Ichiro Fujita Sumio Miyazaki Yuhei Hamasaki Shuki Mizutani
Publish Date: 2002/07/01
Volume: 76, Issue: 1, Pages: 74-79
Abstract
The correlation between infant leukemia and in utero exposure to topoisomerase II topoII inhibitor has been clarified We examined the in vitro effect of topoII inhibitor etoposide on cleavage of theMLL gene in cord and peripheral blood mononuclear cells MNCs Southern blot analysis showed cleavage of theMLL gene in peripheral blood MNCs of infants when the MNCs were exposed to etoposide MNCs were incubated with etoposide at various concentrations 1 to 50 µM and a ligationmediated polymerase chain reaction LMPCR was used to detect double strand breaks DSBs of DNA in intron 8 of theMLL breakpoint cluster region PCR products obtained with LMPCR were subcloned and sequenced to identify the breakpoint in theMLL gene The PCR products indicated DSBs of theMLL gene were obtained without any difference in the incidence between 3 different samples cord and peripheral blood from infants and children Sequencing analysis showed that the DSBs occurred on the telomeric side of intron 8 and near exon 9 There was no evidence that the cord blood was more susceptible toMLL DNA breakage by topoII inhibitor than were other cells Instability of the partner gene during the fetal period could be associated with the pathogenesis of infant leukemia
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