title: Coexpression of NUP98/TOP1 and TOP1/NUP98 in de novo Acute Myeloid Leukemia with t(11;20)(p15;q12) and t(2;5)(q33;q31).
abstract: The t(11;20)(p15;q11∼12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11;20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]. Expression of the NUP98/TOP1 fusion transcript was confirmed: NUP98 exon 13 was in-frame fused with TOP1 exon 8. The reciprocal TOP1/NUP98 fusion transcript was also detected: TOP1 exon 7 was fused with NUP98 exon 14. After achieving hematological complete remission, the karyotype converted to 46,XY,t(2;5)(q33;q31)[19]/46,sl,t(11;20)(p15;q12)[1]. FISH analysis demonstrated that the 5q31 breakpoint of t(2;5) was centromeric to EGR1. In all 10 cases described in the literature, the NUP98 exon 13/TOP1 exon 8 fusion transcript was expressed, indicating that it may be responsible for the pathogenesis of MDS/AML with t(11;20). On the other hand, the TOP1/NUP98 transcript was coexpressed in 4 cases of de novo AML, but not in 3 cases of therapy-related MDS. Thus, this reciprocal fusion may be associated with progression to AML.
authors.affiliation: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Minami
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Yakushijin
authors.forename: Yu
authors.initials: Y
authors.lastname: Mizutani
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Inui
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Matsui
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamachi
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002880:Chromosomes, Human, Pair 11; D002889:Chromosomes, Human, Pair 2; D002890:Chromosomes, Human, Pair 20; D002895:Chromosomes, Human, Pair 5; D004264:DNA Topoisomerases, Type I / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D032681:Spectral Karyotyping; D014178:Translocation, Genetic
chemical_list: D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human