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Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development

Authors :
Neil A. Barrett
Camille Malouf
Chrysa Kapeni
Wendi A. Bacon
George Giotopoulos
Sten Eirik W. Jacobsen
Brian J. Huntly
Katrin Ottersbach
Source :
Cell Reports, Vol 16, Iss 4, Pp 1039-1054 (2016)
Publication Year :
2016
Publisher :
Elsevier, 2016.

Abstract

MLL-AF4+ infant B cell acute lymphoblastic leukemia is characterized by an early onset and dismal survival. It initiates before birth, and very little is known about the early stages of the disease’s development. Using a conditional Mll-AF4-expressing mouse model in which fusion expression is targeted to the earliest definitive hematopoietic cells generated in the mouse embryo, we demonstrate that Mll-AF4 imparts enhanced B lymphoid potential and increases repopulation and self-renewal capacity during a putative pre-leukemic state. This occurs between embryonic days 12 and 14 and manifests itself most strongly in the lymphoid-primed multipotent progenitor population, thus pointing to a window of opportunity and a potential cell of origin. However, this state alone is insufficient to generate disease, with the mice succumbing to B cell lymphomas only after a long latency. Future analysis of the molecular details of this pre-leukemic state will shed light on additional events required for progression to acute leukemia.

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
22111247
Volume :
16
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.6876b78c7636415d93054bf2cab58c7a
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2016.06.046