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MLL-AF4 fusion is the most common consequence of chromosomal translocations in infant leukaemia and is associated with a 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.

Original publication

DOI

10.1038/sj.onc.1209636

Type

Journal article

Journal

Oncogene

Publication Date

25/05/2006

Volume

25

Pages

3093 - 3103

Keywords

Animals, B-Lymphocytes, Cell Lineage, Cell Transformation, Neoplastic, Female, Genes, Lethal, Homeodomain Proteins, Humans, Integrases, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Male, Mice, Mice, Inbred C57BL, Myeloid-Lymphoid Leukemia Protein, Oncogene Proteins, Fusion, Phenotype, T-Lymphocytes