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Gatekeeper function of the RUNX1 transcription factor in acute leukemia

Niebuhr, Birte; Fischer, Meike; Taeger, Maike; Cammenga, Jörg LU and Stocking, Carol (2008) In Blood Cells, Molecules & Diseases 40(2). p.211-218
Abstract
The RUNX1 gene encodes the alpha subunit of the core binding factor (CBF) and 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 hematopoietic progenitors with increased self-renewal potential 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 supports 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... (More)
The RUNX1 gene encodes the alpha subunit of the core binding factor (CBF) and 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 hematopoietic progenitors with increased self-renewal potential 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 supports 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 or fusion partner. A number of different approaches have led to the identification of secondary events that lead to the overt acute phase; however, the majority is unknown. Finally, the concept of the "leukemia stern cell" and its therapeutic importance is discussed in light of the RUNX1 gatekeeper function. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
self-renewal, differentiation, leukemia stem cell, core-binding factor
in
Blood Cells, Molecules & Diseases
volume
40
issue
2
pages
211 - 218
publisher
Elsevier
external identifiers
  • wos:000253474400012
  • scopus:38949105508
ISSN
1096-0961
DOI
10.1016/j.bcmd.2007.07.018
language
English
LU publication?
yes
id
f2b7b5a8-d87b-450f-b9b1-51ce8282598e (old id 1193870)
date added to LUP
2008-09-10 09:41:54
date last changed
2017-01-01 04:23:51
@article{f2b7b5a8-d87b-450f-b9b1-51ce8282598e,
  abstract     = {The RUNX1 gene encodes the alpha subunit of the core binding factor (CBF) and 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 hematopoietic progenitors with increased self-renewal potential 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 supports 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 or fusion partner. A number of different approaches have led to the identification of secondary events that lead to the overt acute phase; however, the majority is unknown. Finally, the concept of the "leukemia stern cell" and its therapeutic importance is discussed in light of the RUNX1 gatekeeper function.},
  author       = {Niebuhr, Birte and Fischer, Meike and Taeger, Maike and Cammenga, Jörg and Stocking, Carol},
  issn         = {1096-0961},
  keyword      = {self-renewal,differentiation,leukemia stem cell,core-binding factor},
  language     = {eng},
  number       = {2},
  pages        = {211--218},
  publisher    = {Elsevier},
  series       = {Blood Cells, Molecules & Diseases},
  title        = {Gatekeeper function of the RUNX1 transcription factor in acute leukemia},
  url          = {http://dx.doi.org/10.1016/j.bcmd.2007.07.018},
  volume       = {40},
  year         = {2008},
}