Leading science, pioneering therapies
CRM Publications

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

TitleMll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development.
Publication TypeJournal Article
Year of Publication2016
AuthorsBarrett NA, Malouf C, Kapeni C, Bacon WA, Giotopoulos G, Jacobsen SEirik W, Huntly BJ, Ottersbach K
JournalCell Rep
Volume16
Issue4
Pagination1039-54
Date Published2016 Jul 26
ISSN2211-1247
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.

DOI10.1016/j.celrep.2016.06.046
Alternate JournalCell Rep
PubMed ID27396339
PubMed Central IDPMC4967476
Publication institute
CRM