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

M Metzler, A Forster, R Pannell, M J Arends, A Daser, M N Lobato, T H Rabbitts

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)3093-103
Number of pages11
Issue number22
Publication statusPublished - 25 May 2006


  • 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


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