Gatekeeper function of the RUNX1 transcription factor in acute leukemia
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1193870
- author
- Niebuhr, Birte ; Fischer, Meike ; Taeger, Maike ; Cammenga, Jörg LU and Stocking, Carol
- organization
- publishing date
- 2008
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hematology/Transplantation (013022014)
- id
- f2b7b5a8-d87b-450f-b9b1-51ce8282598e (old id 1193870)
- date added to LUP
- 2016-04-01 11:38:25
- date last changed
- 2022-04-28 17:49:41
@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}},
keywords = {{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}},
doi = {{10.1016/j.bcmd.2007.07.018}},
volume = {{40}},
year = {{2008}},
}