A conditional model of MLL-AF4 B-cell tumourigenesis using invertor technology.

Journal article

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.

Authors: Metzler, M; Forster, A; Pannell, R; Arends, M; Daser, A

• Journal: Oncogene
• Volume: 25
• Issue: 22
• Pages: 3093-3103
• Publication date: 2006-05-01
• DOI: 10.1038/sj.onc.1209636
• EISSN: 1476-5594
• ISSN: 0950-9232
• Language: English
• Keywords: Cell Lineage; Humans; Mice; Cell Transformation, Neoplastic; B-Lymphocytes; Animals; Female; Mice, Inbred C57BL; Male; Homeodomain Proteins; Genes, Lethal; Lymphoma, Large B-Cell, Diffuse; Phenotype; T-Lymphocytes; Integrases; Oncogene Proteins, Fusion; Myeloid-Lymphoid Leukemia Protein; Lymphoma, B-Cell