Journal
ONCOGENE
Volume 25, Issue 22, Pages 3093-3103Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1209636
Keywords
MLL; AF4; chromosomal translocations; invertor model; Cre-loxP; leukaemia
Funding
- Medical Research Council [G0600914] Funding Source: researchfish
- Medical Research Council [G0600914] Funding Source: Medline
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MLL-AF4 fusion is the most common consequence of chromosomal translocations in infant leukaemia and is associated witha poor prognosis. MLL-AF4 is thought to be required in haematopoietic stem cells to elicit leukaemia and may be involved in tumour phenotype specification as it is only found in B-cell tumours in humans. We have employed the invertor conditional technology to create a model of MLL-AF4, in which a floxed AF4 cDNA was knocked into Mll in the opposite orientation for transcription. Cell-specific Cre expression was used to generate Mll-AF4 expression. The mice develop exclusively B-cell lineage neoplasias, whether the Cre gene was controlled by B- or T-cell promoters, but of a more mature phenotype than normally observed in childhood leukaemia. These findings show that the MLL-AF4 fusion protein does not have a mandatory role in multi-potent haematopoietic stem cells to cause cancer and indicates that MLL-AF4 has an instructive function in the phenotype of the tumour.
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