Premium
Tumorigenesis in mice with a fusion of the leukaemia oncogene Mll and the bacterial lacZ gene
Author(s) -
Dobson Claire L.,
Warren Alan J.,
Pannell Richard,
Forster Alan,
Rabbitts Terence H.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.5.843
Subject(s) - nucleic acid , biology , genetics
Many different chromosomal translocations occur in man at chromosome 11q23 in acute leukaemias. Molecular analyses revealed that the MLL gene (also called ALL‐1 , HRX or HTRX ) is broken by the translocations, causing fusion with genes from other chromosomes. The diversity of MLL fusion partners poses a dilemma about the function of the fusion proteins in tumour development. The consequence of MLL truncation and fusion has been analysed by joining exon 8 of Mll with the bacterial lacZ gene using homologous recombination in mouse embryonic stem cells. We show that this fusion is sufficient to cause embryonic stem cell‐derived acute leukaemias in chimeric mice, and these tumours occur with long latency compared with those found in MLL–Af9 chimeric mice. These findings indicate that an MLL fusion protein can contribute to tumorigenesis, even if the fusion partner has no known pathogenic role. Thus, truncation and fusion of MLL can be sufficient for tumorigenesis, regardless of the fusion partner.