Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Initiation of MLL-rearranged AML is dependent on C/EBPα

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Autocrine VEGF-VEGFR2-Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. The splicing factor RBM25 controls MYC activity in acute myeloid leukemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. BloodSpot: a database of healthy and malignant haematopoiesis updated with purified and single cell mRNA sequencing profiles

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Leukemogenic nucleophosmin mutation disrupts the transcription factor hub regulating granulo-monocytic fates

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations
MLL-fusion proteins are potent inducers of oncogenic transformation, and their expression is considered to be the main oncogenic driving force in ∼10% of human acute myeloid leukemia (AML) patients. These oncogenic fusion proteins are responsible for the initiation of a downstream transcriptional program leading to the expression of factors such as MEIS1 and HOXA9, which in turn can replace MLL-fusion proteins in overexpression experiments. To what extent MLL fusion proteins act on their own during tumor initiation, or if they collaborate with other transcriptional regulators, is unclear. Here, we have compared gene expression profiles from human MLL-rearranged AML to normal progenitors and identified the myeloid tumor suppressor C/EBPα as a putative collaborator in MLL-rearranged AML. Interestingly, we find that deletion of Cebpa rendered murine hematopoietic progenitors completely resistant to MLL-ENL-induced leukemic transformation, whereas C/EBPα was dispensable in already established AMLs. Furthermore, we show that Cebpa-deficient granulocytic-monocytic progenitors were equally resistant to transformation and that C/EBPα collaborates with MLL-ENL in the induction of a transcriptional program, which is also apparent in human AML. Thus, our studies demonstrate a key role of C/EBPα in MLL fusion-driven transformation and find that it sharply demarcates tumor initiation and maintenance.
Original languageEnglish
JournalJournal of Experimental Medicine
Volume211
Issue number1
Pages (from-to)5-13
ISSN0022-1007
DOIs
Publication statusPublished - 13 Jan 2014

ID: 42185225