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

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

  1. The frequency and severity of epistaxis in children with sickle cell anaemia in eastern Uganda: a case-control study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Lack of topoisomerase copy number changes in patients with de novo and relapsed diffuse large B-cell lymphoma

    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
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)882-93
ISSN0301-472X
DOIs
Publication statusPublished - 2 Jul 2013

ID: 38945858