Hematopoietic Stem Cell Expansion Precedes the Generation of Committed Myeloid Leukemia-initiating Cells in C/EBP alpha Mutant AML
(2009) In Cancer Cell 16(5). p.390-400- Abstract
- We here use knockin mutagenesis in the mouse to model the spectrum of acquired CEBPA mutations in human acute myeloid leukemia. We find that C-terminal C/EBP alpha mutations increase the proliferation of long-term hematopoietic stem cells (LT-HSCs) in a cell-intrinsic manner and override normal HSC homeostasis, leading to expansion of premalignant HSCs. However, such mutations impair myeloid programming of HSCs and block myeloid lineage commitment when homozygous. In contrast, N-terminal C/EBP alpha mutations are silent with regards to HSC expansion, but allow the formation of committed myeloid progenitors, the templates for leukemia-initiating cells. The combination of N- and C-terminal C/EBP alpha mutations incorporates both features,... (More)
- We here use knockin mutagenesis in the mouse to model the spectrum of acquired CEBPA mutations in human acute myeloid leukemia. We find that C-terminal C/EBP alpha mutations increase the proliferation of long-term hematopoietic stem cells (LT-HSCs) in a cell-intrinsic manner and override normal HSC homeostasis, leading to expansion of premalignant HSCs. However, such mutations impair myeloid programming of HSCs and block myeloid lineage commitment when homozygous. In contrast, N-terminal C/EBP alpha mutations are silent with regards to HSC expansion, but allow the formation of committed myeloid progenitors, the templates for leukemia-initiating cells. The combination of N- and C-terminal C/EBP alpha mutations incorporates both features, accelerating disease development and explaining the clinical prevalence of this configuration of CEBPA mutations. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1519566
- author
- Bereshchenko, Oxana ; Mancini, Elena ; Moore, Susan ; Bilbao, Daniel ; Månsson, Robert LU ; Luc, Sidinh ; Grover, Amit ; Jacobsen, Sten Eirik W LU ; Bryder, David LU and Nerlov, Claus
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer Cell
- volume
- 16
- issue
- 5
- pages
- 390 - 400
- publisher
- Cell Press
- external identifiers
-
- wos:000271755100008
- scopus:70350497395
- ISSN
- 1878-3686
- DOI
- 10.1016/j.ccr.2009.09.036
- language
- English
- LU publication?
- yes
- id
- 70255314-147d-40f7-a2fc-3b5d4e384676 (old id 1519566)
- date added to LUP
- 2016-04-01 12:24:19
- date last changed
- 2022-07-30 02:16:25
@article{70255314-147d-40f7-a2fc-3b5d4e384676, abstract = {{We here use knockin mutagenesis in the mouse to model the spectrum of acquired CEBPA mutations in human acute myeloid leukemia. We find that C-terminal C/EBP alpha mutations increase the proliferation of long-term hematopoietic stem cells (LT-HSCs) in a cell-intrinsic manner and override normal HSC homeostasis, leading to expansion of premalignant HSCs. However, such mutations impair myeloid programming of HSCs and block myeloid lineage commitment when homozygous. In contrast, N-terminal C/EBP alpha mutations are silent with regards to HSC expansion, but allow the formation of committed myeloid progenitors, the templates for leukemia-initiating cells. The combination of N- and C-terminal C/EBP alpha mutations incorporates both features, accelerating disease development and explaining the clinical prevalence of this configuration of CEBPA mutations.}}, author = {{Bereshchenko, Oxana and Mancini, Elena and Moore, Susan and Bilbao, Daniel and Månsson, Robert and Luc, Sidinh and Grover, Amit and Jacobsen, Sten Eirik W and Bryder, David and Nerlov, Claus}}, issn = {{1878-3686}}, language = {{eng}}, number = {{5}}, pages = {{390--400}}, publisher = {{Cell Press}}, series = {{Cancer Cell}}, title = {{Hematopoietic Stem Cell Expansion Precedes the Generation of Committed Myeloid Leukemia-initiating Cells in C/EBP alpha Mutant AML}}, url = {{http://dx.doi.org/10.1016/j.ccr.2009.09.036}}, doi = {{10.1016/j.ccr.2009.09.036}}, volume = {{16}}, year = {{2009}}, }