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Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23)
Author(s) -
Dahéron Laurence,
Veinstein Anne,
Brizard Françoise,
Drabkin Harry,
Lacotte Laurence,
Guilhot François,
Larsen Christian Jacques,
Brizard André,
Roche Joelle
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.1157
Subject(s) - biology , exon , microbiology and biotechnology , gene , genetics , leucine zipper , leukemia , fusion protein , breakpoint , fusion gene , gene rearrangement , intron , chromosomal translocation , peptide sequence , recombinant dna
The mixed lineage leukemia, MLL , gene is frequently rearranged in patients with secondary leukemia following treatment with DNA topoisomerase II inhibitors. 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 lymphoma. 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 MLL‐LPP transcripts, which fuse MLL exon 8 to LPP exon 9, were detected by RT‐PCR, although the smaller of these contained a deletion of 120 bp from the 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 domains of LPP. A reciprocal LPP‐MLL transcript, predicted to include the proline‐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 partner in secondary leukemia resulting from topoisomerase inhibitors. The MLL‐LPP and LPP‐MLL predicted proteins contain many of the features present in other MLL rearrangements. © 2001 Wiley‐Liss, Inc.