Leukaemia lineage specification caused by cell-specific Mll-Enl translocations.

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

Oncogene

journal_title

Oncogene

authors

Cano F,Drynan LF,Pannell R,Rabbitts TH

doi

10.1038/sj.onc.1210818

subject

Has Abstract

pub_date

2008-03-20 00:00:00

pages

1945-50

issue

13

eissn

0950-9232

issn

1476-5594

pii

1210818

journal_volume

27

pub_type

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