FUSION OF THE NUCLEOPORIN GENE NUP98 TO HOXA9 BY THE CHROMOSOME-TRANSLOCATION T(7-11)(P15-P15) IN HUMAN MYELOID-LEUKEMIA

Expression of Hoxa7 and Hoxa9 is activated by proviral integration in BXH2 murine myeloid leukaemias. This result, combined with the mapping of the HOXA, locus to human chromosome 7p15, suggested that one of th e HOXA genes might be involved in the t(7;11)(p15;p15) translocation f ound in some human myeloid leukaemia patients. Here we show that in th ree patients with t(7;11), the chromosome rearrangement creates a geno mic fusion between the HOXA9 gene and the nucleoporin gene NUP98 on ch romosome 11p15. The translocation produces an invariant chimaeric NUP9 8/HOXA9 transcript containing the amino terminal half of NUP98 fused i n frame to HOXA9. These studies identify HOXA9 as an important human m yeloid leukaemia gene and suggest an important role for nucleoporins i n human myeloid leukaemia given that a second nucleoporin, NUP214, has also been implicated in human myeloid leukaemia.