Lack of the p42 form of C/EBPα leads to spontaneous immortalization and lineage infidelity of committed myeloid progenitors

Research output: Contribution to journalJournal articleResearchpeer-review

Acute myeloid leukemia (AML) develops via a multistep process involving several genetic and epigenetic events, which ultimately leads to the formation of a heterogeneous population of malignant cells, of which only a small subpopulation termed the leukemia initiating cell (LIC) is able to sustain the leukemia. The identity of the LIC is highly diverse and ranges from populations resembling hematopoietic stem cells or multipotent progenitors (MPPs) to more committed myeloid progenitors, and the question still remains whether this is a direct consequence of which cells are targets of the final transforming events. In this study, we use premalignant cells from a Cebpa mutant AML model, in which the LIC population resembles granulocyte-macrophage progenitors (GMPs), to show that premalignant GMPs undergo spontaneous immortalization with a high clonal frequency when cultured in vitro, suggesting that these cells constitute the target of the final transforming events. Furthermore, we show that premalignant GMPs are characterized by a distinct T cell gene expression signature correlating with an increased potential for differentiation toward the T cell lineage. These findings have implications for our understanding of the transcriptional wiring in premalignant myeloid progenitors and how this contributes to the development of AML.
Original languageEnglish
JournalExperimental Hematology
Volume41
Issue number10
Pages (from-to)882-893
Number of pages12
ISSN0301-472X
DOIs
Publication statusPublished - Oct 2013

    Research areas

  • Animals, CCAAT-Enhancer-Binding Protein-alpha, Cell Differentiation, Cell Lineage, Cell Proliferation, Cells, Cultured, Gene Expression Regulation, Genetic Variation, Leukemia, Myeloid, Acute, Mice, Mutation, Myeloid Progenitor Cells, Phenotype, Time Factors

ID: 108144302