Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Schuster, Mikkel B1
  • Frank, Anne-Katrine
  • Bagger, Frederik O
  • Rapin, Nicolas
  • Vikesaa, Jonas
  • Porse, Bo T
  • 1 The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark; Danish Stem Cell Center, Faculty of Health Sciences, University of Copenhagen, Denmark. , (Denmark)
Type
Published Article
Journal
Experimental hematology
Publication Date
October 2013
Volume
41
Issue
10
Identifiers
DOI: 10.1016/j.exphem.2013.06.003
PMID: 23831605
Source
Medline
License
Unknown

Abstract

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.

Report this publication

Statistics

Seen <100 times