Loss of C/EBP alpha cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage

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Bibtex

@article{5d33a706379141e2825b0050d39bc9af,
title = "Loss of C/EBP alpha cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage",
abstract = "CCAAT/enhancer binding protein (C/EBP)alpha is a myeloid-specific transcription factor that couples lineage commitment to terminal differentiation and cell cycle arrest, and is found mutated in 9{\%} of patients who have acute myeloid leukemia (AML). We previously showed that mutations which dissociate the ability of C/EBP alpha to block cell cycle progression through E2F inhibition from its function as a transcriptional activator impair the in vivo development of the neutrophil granulocyte and adipose lineages. We now show that such mutations increase the capacity of bone marrow ( BM) myeloid progenitors to proliferate, and predispose mice to a granulocytic myeloproliferative disorder and transformation of the myeloid compartment of the BM. Both of these phenotypes were transplantable into lethally irradiated recipients. BM transformation was characterized by a block in granulocyte differentiation, accumulation of myeloblasts and promyelocytes, and expansion of myeloid progenitor populations - all characteristics of AML. Circulating myeloblasts and hepatic leukocyte infiltration were observed, but thrombocytopenia, anemia, and elevated leukocyte count - normally associated with AML - were absent. These results show that disrupting the cell cycle regulatory function of C/EBP alpha is sufficient to initiate AML-like transformation of the granulocytic lineage, but only partially the peripheral pathology of AML.",
author = "BT Porse and David Bryder and K Theilgaard-Monch and MS Hasemann and Kristina Anderson and I Damgaard and Jacobsen, {Sten Eirik W} and C Nerlov",
year = "2005",
doi = "10.1084/jem.20050067",
language = "English",
volume = "202",
pages = "85--96",
journal = "Journal of Experimental Medicine",
issn = "1540-9538",
publisher = "Rockefeller University Press",
number = "1",

}