THE INV(11)(P15Q22) CHROMOSOME-TRANSLOCATION OF DE-NOVO AND THERAPY-RELATED MYELOID MALIGNANCIES RESULTS IN FUSION OF THE NUCLEOPORIN GENE,NUP98, WITH THE PUTATIVE RNA HELICASE GENE, DDX10

The inv(11)(p15q22) is a recurrent chromosomal abnormality associated with de novo and therapy-related myeloid malignancies. Here we report the molecular definition of this chromosomal aberration in four patien ts, Positional cloning showed the consistent rearrangement of the DDX1 0 gene on chromosome 11q22, which encodes a putative RNA helicase, The translocation targets the NUP98 gene on 11p15, a member of the FG pep tide repeat nucleoporin family. In DDX10 and NUP98, the inv(ll) breakp oints occurred within two introns of each gene and the two genes merge d in-frame to produce the chimeric transcripts characteristic of this translocation. Although two reciprocal chimeric products, NUP98-DDX10 and DDX10-NUP98, were predicted, only NUP98-DDX10 appears to be implic ated in tumorigenesis, DDX10 is predicted to be involved in ribosome a ssembly. NUP98 has been identified as a nuclear pore complex protein a nd a target of chromosomal translocation in acute myeloid leukemia thr ough the t(7;11)(p15;p15) translocation. The predicted NUP98-DDX10 fus ion protein may promote leukemogenesis through aberrant nucleoplasmic transport of mRNA or alterations in ribosome assembly. (C) 1997 by The American Society of Hematology.