Advertisement

The RUNX1 Transcription Factor: A Gatekeeper in Acute Leukemia

  • Carol Stocking
  • Birte Niebuhr
  • Meike Fischer
  • Maike Täger
  • Jörg Cammenga
Conference paper
Part of the NATO Science for Peace and Security Series A: Chemistry and Biology book series (NAPSA)

The RUNX1 gene, which encodes a transcription factor, is a common target of genetic mutations in acute leukemia. We propose that RUNX1 is a gatekeeper gene, the disruption of which leads to the exodus of a subset of selfrenewing “stem” cells from the normal environmental controls of homeostasis. This pool of “escaped” cells is the target of secondary mutations, accumulating over time to induce the aggressive manifestation of acute leukemia. Evidence from patient and animal studies support the concept that RUNX1 mutations are the initiating event in different leukemia subtypes, but also suggests that diverse mechanisms are used to subvert RUNX1 function. One common result is the inhibition of differentiation – but its effect impinges on different lineages and stages of differentiation, depending on the mutation. A number of different approaches have led to the identification of a few secondary events that lead to the overt acute phase, however, the majority are unknown. Finally, the concept of the “leukemic stem cell” and its therapeutic importance is discussed in light of the RUNX1 gatekeeper function. Key words: leukemic stem cell, core-binding factor, differentiation, self-renewal

Keywords

Acute Myeloid Leukemia Cancer Stem Cell Acute Leukemia Acute Myelogenous Leukemia Secondary Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer 2008

Authors and Affiliations

  • Carol Stocking
    • 1
  • Birte Niebuhr
    • 1
  • Meike Fischer
    • 1
  • Maike Täger
    • 1
  • Jörg Cammenga
    • 2
  1. 1.Heinrich-Pette-Institute for Experimental Virology and ImmunologyGermany
  2. 2.Molecular Medicine and Gene Therapy, Institute of Laboratory MedicineLund University HospitalSweden

Personalised recommendations