THE T(7-11)(P15-P15) TRANSLOCATION IN ACUTE MYELOID-LEUKEMIA FUSES THE GENES FOR NUCLEOPORIN NUP98 AND CLASS-I HOMEOPROTEIN HOXA9

The t(7;11)(p15;p15) translocation is a recurrent chromosomal abnormal ity associated primarily with acute myeloid leukaemia (FAB M2 and M4). We present here the molecular definition of this translocation. On ch romosome 7 positional cloning revealed the consistent rearrangement of the HOXA9 gene, which encodes a class I homeodomain protein potential ly involved in myeloid differentiation. On chromosome 11 the transloca tion targets the human homologue of NUP98, a member of the GLFG nucleo porin family. Chimaeric messages spliced over the breakpoint fuse the GLFG Massachusetts repeat domains of NUP98 in-frame to the HOXA9 homeo box. The predicted NUP98-HOXA9 fusion protein may promote leukaemogene sis through inhibition of HOXA9-mediated terminal differentiation and/ or aberrant nucleocytoplasmic transport.