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Mll fusions generated by Cre‐ loxP‐ mediated de novo translocations can induce lineage reassignment in tumorigenesis
Author(s) -
Drynan Lesley F,
Pannell Richard,
Forster Alan,
Chan Nicole MM,
Cano Florencia,
Daser Angelika,
Rabbitts Terence H
Publication year - 2005
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 - 10.1038/sj.emboj.7600760
Subject(s) - biology , chromosomal translocation , haematopoiesis , carcinogenesis , progenitor cell , stem cell , cancer research , myeloid , induced pluripotent stem cell , genetics , microbiology and biotechnology , embryonic stem cell , gene
Chromosomal translocations are primary events in tumorigenesis. Those involving the mixed lineage leukaemia ( MLL ) gene are found in various guises and it is unclear whether MLL fusions can affect haematopoietic differentiation. We have used a model in which chromosomal translocations are generated in mice de novo by Cre‐ loxP ‐mediated recombination (translocator mice) to compare the functionally relevant haematopoietic cell contexts for Mll fusions, namely pluripotent stem cells, semicommitted progenitors or committed cells. Translocations between Mll and Enl or Af9 cause myeloid neoplasias, initiating in pluripotent stem cells or multipotent myeloid progenitors. However, while Mll‐Enl translocations can also cause leukaemia from T‐cell progenitors, no tumours arose with Mll‐Af9 translocations in the T‐cell compartment. Furthermore, Mll‐Enl translocations in T‐cell progenitors can cause lineage reassignment into myeloid tumours. Therefore, a permissive cellular environment is required for oncogenicity of Mll ‐associated translocations and Mll fusions can influence haematopoietic lineage commitment.