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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.

Original publication

DOI

10.1016/j.ccr.2008.02.008

Type

Journal article

Journal

Cancer Cell

Publication Date

04/2008

Volume

13

Pages

299 - 310

Keywords

Animals, CCAAT-Enhancer-Binding Protein-alpha, Cell Differentiation, Disease Progression, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Granulocytes, Leukemia, Myelomonocytic, Acute, Macrophage-1 Antigen, Mice, Mice, Knockout, Models, Biological, Mutant Proteins, Myeloid Progenitor Cells, Neoplasm Transplantation, Neoplastic Stem Cells, Phenotype, Protein Isoforms, Proto-Oncogene Proteins c-kit