Borrow J, Shearman A M, Stanton V P, Becher R, Collins T, Williams A J, Dubé I, Katz F, Kwong Y L, Morris C, Ohyashiki K, Toyama K, Rowley J, Housman D E
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Nat Genet. 1996 Feb;12(2):159-67. doi: 10.1038/ng0296-159.
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.
t(7;11)(p15;p15)易位是一种常见的染色体异常，主要与急性髓系白血病（FAB M2和M4）相关。我们在此展示这种易位的分子定义。在7号染色体上，定位克隆揭示了HOXA9基因的一致重排，该基因编码一种可能参与髓系分化的I类同源结构域蛋白。在11号染色体上，易位靶向NUP98的人类同源物，NUP98是GLFG核孔蛋白家族的成员。跨越断点拼接的嵌合信息将NUP98的GLFG重复结构域读框内融合到HOXA9同源框。预测的NUP98-HOXA9融合蛋白可能通过抑制HOXA9介导的终末分化和/或异常的核质运输促进白血病发生。
