Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells

Kirstetter, Peggy; Schuster, Mikkel B; Bereshchenko, Oksana; Moore, Susan; Dvinge, Heidi; Kurz, Elke; Theilgaard-Mönch, Kim; Månsson, Robert; Pedersen, Thomas A; Pabst, Thomas; Schrock, Evelin; Porse, Bo T; Jacobsen, Sten Eirik W; Bertone, Paul; Tenen, Daniel G; Nerlov, Claus (2008). Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. Cancer cell, 13(4), pp. 299-310. Cambridge, Mass.: Cell Press 10.1016/j.ccr.2008.02.008

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Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBPalpha isoform (p42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete penetrance. p42-deficient leukemia could be transferred by a Mac1+c-Kit+ population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1+c-Kit+ progenitors revealed a signature shared with MLL-AF9-transformed AML.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Pabst, Thomas

ISSN:

1535-6108

ISBN:

18394553

Publisher:

Cell Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:02

Last Modified:

17 Mar 2015 22:15

Publisher DOI:

10.1016/j.ccr.2008.02.008

PubMed ID:

18394553

Web of Science ID:

000254817400005

URI:

https://boris.unibe.ch/id/eprint/27100 (FactScience: 102230)

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