The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9.
The t(7;11)(p15;p15) translocation is a recurrent chromosomal abnormality associated primarily with acute myeloid leukaemia (FAB M2 and M4). We present here the molecular definition of this translocation. On chromosome 7 positional cloning revealed the consistent rearrangement of the HOXA9 gene, which encodes a class I homeodomain protein potentially involved in myeloid differentiation. On chromosome 11 the translocation targets the human homologue of NUP98, a member of the GLFG nucleoporin family. Chimaeric messages spliced over the breakpoint fuse the GLFG repeat domains of NUP98 in-frame to the HOXA9 homeobox. The predicted NUP98-HOXA9 fusion protein may promote leukaemogenesis through inhibition of HOXA9-mediated terminal differentiation and/or aberrant nucleocytoplasmic transport.
Borrow
J
J
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Shearman
A M
AM
Stanton
V P
VP
Becher
R
R
Collins
T
T
Williams
A J
AJ
Dubé
I
I
Katz
F
F
Kwong
Y L
YL
Morris
C
C
Ohyashiki
K
K
Toyama
K
K
Rowley
J
J
Housman
D E
DE
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
D018398:Homeodomain Proteins; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C097899:homeobox protein HOXA9; C093350:nuclear pore complex protein 98