Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23)

The mixed lineage leukemia, MLL, gene is frequently rearranged in patients with secondary leukemia following treatment with DNA topoisomerase II inhib itors. By FISH and Southern blot analyses we identified a rearrangement in the MLL gene due to a novel t(3;11)(q28;q23) chromosomal translocation in a patient who developed AML-M5 3 years after treatment for a follicular lymp homa. Through inverse PCR, the LPP (lipoma preferred partner) gene on 3q28 was identified as the MLL fusion partner. LPP contains substantial identity to the focal adhesion protein, zyxin, and is frequently fused to HMGIC in lipomas. The breakpoint occurred in intron 8 of MLL and LPP. Two in-frame M LL-LPP transcripts, which fuse MLL exon 8 to LPP exon 9, were detected by R T-PCR, although the smaller of these contained a deletion of 120 bp from th e MLL sequence. The predicted MLL-LPP fusion protein includes the A/T hook motifs and methyltransferase domain of MLL joined to the two last LIM domai ns of LPP. A reciprocal LPP-MLL transcript, predicted to include the prolin e-rich and leucine zipper motifs, and the first LIM domain of LPP were also detected by RT-PCR. In summary, LPP is a newly identified MLL fusion partn er in secondary leukemia resulting from topoisomerase inhibitors. The MLL-L PP and LPP-MLL predicted proteins contain many of the features present in o ther MLL rearrangements. (C) 2001 Wiley-Liss, Inc.