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Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development
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 target...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967476/ https://www.ncbi.nlm.nih.gov/pubmed/27396339 http://dx.doi.org/10.1016/j.celrep.2016.06.046 |
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author | Barrett, Neil A. Malouf, Camille Kapeni, Chrysa Bacon, Wendi A. Giotopoulos, George Jacobsen, Sten Eirik W. Huntly, Brian J. Ottersbach, Katrin |
author_facet | Barrett, Neil A. Malouf, Camille Kapeni, Chrysa Bacon, Wendi A. Giotopoulos, George Jacobsen, Sten Eirik W. Huntly, Brian J. Ottersbach, Katrin |
author_sort | Barrett, Neil A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4967476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49674762016-08-04 Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development Barrett, Neil A. Malouf, Camille Kapeni, Chrysa Bacon, Wendi A. Giotopoulos, George Jacobsen, Sten Eirik W. Huntly, Brian J. Ottersbach, Katrin Cell Rep Article 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. Cell Press 2016-07-07 /pmc/articles/PMC4967476/ /pubmed/27396339 http://dx.doi.org/10.1016/j.celrep.2016.06.046 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Barrett, Neil A. Malouf, Camille Kapeni, Chrysa Bacon, Wendi A. Giotopoulos, George Jacobsen, Sten Eirik W. Huntly, Brian J. Ottersbach, Katrin Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development |
title | Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development |
title_full | Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development |
title_fullStr | Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development |
title_full_unstemmed | Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development |
title_short | Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development |
title_sort | mll-af4 confers enhanced self-renewal and lymphoid potential during a restricted window in development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967476/ https://www.ncbi.nlm.nih.gov/pubmed/27396339 http://dx.doi.org/10.1016/j.celrep.2016.06.046 |
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