Abstract:
:Chromosomal translocations involving the Mixed-Lineage Leukaemia (MLL) gene underlie many human leukaemias and MLL rearrangements are found in both acute myelogenous and acute lymphoblastic leukaemias. To assess the functionally relevant haematopoietic cell contexts for MLL fusions to be tumorigenic, we have generated different lines of mice in which de novo Mll-associated translocations occur. In these models, reciprocal chromosomal translocations occur by means of Cre-loxP-mediated recombination (translocator mice) in different cells of the haematopoietic system (namely haematopoietic stem cells, semi-committed progenitors or committed T or B cells). Translocations between Mll and Enl cause myeloid neoplasias, initiating in stem cells or progenitors while no tumours arose when the translocation was restricted to the B-cell compartment. Despite the absence of tumorigenesis, Mll-Enl translocations did occur and Mll-Enl fusion mRNA was expressed in B-cell-restricted translocators. A permissive cellular environment is therefore required for oncogenicity of Mll-associated translocations since the occurrence of Mll-Enl does not promote unrestricted proliferation in all haematopoietic cellular contexts, consistent with a specific instructive role of the MLL-fusion proteins in leukaemogenesis.
journal_name
Oncogenejournal_title
Oncogeneauthors
Cano F,Drynan LF,Pannell R,Rabbitts THdoi
10.1038/sj.onc.1210818subject
Has Abstractpub_date
2008-03-20 00:00:00pages
1945-50issue
13eissn
0950-9232issn
1476-5594pii
1210818journal_volume
27pub_type
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