t(9;11)(p22;p15) in acute myeloid leukemia results in a fusion between NUP98 and the gene encoding transcriptional coactivators p52 and p75-lens epithelium-derived growth factor (LEDGF)

A t(9;11)(p22;p15) chromosomal translocation was identified in an adult pat ient with de novo acute myelogenous leukemia. Fluorescence in situ hybridiz ation and Southern blot analysis mapped the 11p15 breakpoint to the NUP98 g ene. Using 3' rapid amplification of cDNA ends, we have identified a chimer ic mRNA that fused the NUP98 FXFG repeats in frame to the COOH-terminal por tion of the gene encoding the transcriptional coactivators p52 and p75, als o known as lens epithelium-derived growth factor (LEDGF), As expected, both NUP98-p52 and NUP98-p75 (LEDGF) chimeric mRNAs were detected by reverse tr anscription-PCR; however, the reciprocal p52/p75 (LEDGF)-NUP98 fusion mRNA was not detected. Our results demonstrate that this is the most 5' NUP98 fu sion reported and reveal a previously unrecognized genetic target, the gene encoding p52/p75 (LEDGF).