Linked Life Data

18212737

Source:http://linkedlifedata.com/resource/pubmed/id/18212737

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
27
pubmed:dateCreated
2008-6-19
pubmed:abstractText
Acute myeloid leukemia (AML) cells exposed to genotoxic agents arrest their cell cycle at the G2/M checkpoint and are inherently chemoresistant. To understand the mechanism of this chemoresistance, we compared the ability of immature CD34+ versus mature CD34- AML cell lines (KG1a and U937, respectively) to recover from a DNA damage-induced cell cycle checkpoint in G2. Here, we report that KG1a cells have a more stringent G2/M checkpoint response than U937 cells. We show that in both cell types, the CDC25B phosphatase participates in the G2/M checkpoint recovery and that its expression is upregulated. Furthermore, we show that CHK1 inhibition by UCN-01 in immature KG1a cells allows checkpoint exit and induces sensitivity to genotoxic agents. Similarly, UCN-01 treatment potentializes genotoxic-induced inhibition of colony formation efficiency of primary leukemic cells from AML patients. Altogether, our results demonstrate that checkpoint stringency varies during the maturation process and indicate that targeting checkpoint mechanisms might represent an attractive therapeutic opportunity for chemoresistant immature AML cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3811-20
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
G2/M checkpoint stringency is a key parameter in the sensitivity of AML cells to genotoxic stress.
pubmed:affiliation
LBCMCP-CNRS UMR5088-IFR109 Institut d'Exploration Fonctionnelle des Génomes, University of Toulouse, Toulouse, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't