Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells.
Research output: Contribution to journal › Journal article › Research › peer-review
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 language | English |
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Journal | Cancer Cell |
Volume | 13 |
Issue number | 4 |
Pages (from-to) | 299-310 |
Number of pages | 11 |
ISSN | 1535-6108 |
DOIs | |
Publication status | Published - 2008 |
Bibliographical note
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
ID: 5140496