RAPID COMMUNICATION 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 location. Although two reciprocal chimeric products, NUP98DDX10 and DDX10-NUP98, were predicted, only NUP98associated with de novo and therapy-related myeloid malignancies. Here we report the molecular definition of this chroDDX10 appears to be implicated in tumorigenesis. DDX10 is predicted to be involved in ribosome assembly. NUP98 has mosomal aberration in four patients. Positional cloning showed the consistent rearrangement of the DDX10 gene on been identified as a nuclear pore complex protein and a target of chromosomal translocation in acute myeloid leukemia chromosome 11q22, which encodes a putative RNA helicase. The translocation targets the NUP98 gene on 11p15, a memthrough the t(7;11)(p15;p15) translocation. The predicted NUP98-DDX10 fusion protein may promote leukemogenesis ber of the FG peptide repeat nucleoporin family. In DDX10 and NUP98, the inv(11) breakpoints occurred within two inthrough aberrant nucleoplasmic transport of mRNA or alterations in ribosome assembly. trons of each gene and the two genes merged in-frame to produce the chimeric transcripts characteristic of this transq 1997 by The American Society of Hematology.