title: NUP98 is fused to HOXA9 in a variant complex t(7;11;13;17) in a patient with AML-M2.
abstract: The t(7;11)(p15;p15.4) has been reported to fuse the NUP98 gene (11p15), a component of the nuclear pore complex, with the class-1 homeobox gene HOXA9 at 7p15. This translocation has been associated with myeloid leukemias, predominantly acute myeloid leukemia (AML) M2 subtype with trilineage myelodysplastic features, and with a poor prognosis. The derived fusion protein retains the FG repeat motif of NUP98 N-terminus and the homeodomain shared by the HOX genes, acting as an oncogenic transcription factor critical for leukemogenesis. We report here a new complex t(7;11)-variant, i.e., t(7;11;13;17)(p15;p15;p?;p1?2) in a patient with AML-M2 and poor prognosis. The NUP98-HOXA9 fusion transcript was detected by RT-PCR, suggesting its role in the malignant transformation as it has been postulated for other t(7;11)-associated leukemias. No other fusion transcripts involving the NUP98 or HOXA9 genes were present, although other mechanisms involving several genes on chromosomes 13 and 17 may also be involved. To our knowledge, this is the first t(7;11) variant involving NUP98 described in hematological malignancies.
authors.affiliation: Department of Genetics, School of Science, University of Navarra, C/ Irunlarrea s/n, 31008-Pamplona, Spain. ilahortiga@unav.es
authors.forename: Idoya
authors.initials: I
authors.lastname: Lahortiga
authors.forename: Elena
authors.initials: E
authors.lastname: Belloni
authors.forename: Iria
authors.initials: I
authors.lastname: Vázquez
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: María J
authors.initials: MJ
authors.lastname: Larrayoz
authors.forename: Jose L
authors.initials: JL
authors.lastname: Vizmanos
authors.forename: Mikel
authors.initials: M
authors.lastname: Valgañón
authors.forename: Isabel
authors.initials: I
authors.lastname: Zudaire
authors.forename: Borja
authors.initials: B
authors.lastname: Sáez
authors.forename: María C
authors.initials: MC
authors.lastname: Mateos
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
authors.forename: María J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: María D
authors.initials: MD
authors.lastname: Odero
mesh_terms: D000368:Aged; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D002897:Chromosomes, Human, Pair 7; D005260:Female; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D014178:Translocation, Genetic
chemical_list: D018398:Homeodomain Proteins; C400441:NUP98-HOXA9 fusion protein, human; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; C097899:homeobox protein HOXA9