Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-3-6
pubmed:abstractText
Bone marrow stromal cells (BMSCs) have been found to support leukemic cell survival; however, the mechanisms responsible are far from elucidated yet. Therefore, the effect of BMSCs on both proliferation and apoptosis characteristics of acute myeloid leukaemia (AML) cells was investigated as well as the effect of BMSCs exposure to chemotherapy on the stromal supportive capacity. Leukemic HL-60 and primary AML cells were either untreated or treated with cytarabine and subsequently cultured for 3-4 days, in the presence or absence of untreated or cytarabine-treated BMSCs. The effect on proliferation and apoptosis was investigated with flow cytometry using CFSE labeling and Syto16 and 7AAD staining. BMSCs were found to maintain cytarabine-exposed primary AML cells by protection against spontaneous apoptosis. Accordingly, an increase in phosphorylated-AKT and Bcl-2 expression was found. Concomitant exposure of BMSCs to cytarabine resulted in a dose-dependent decrease of protective capacity of BMSCs. Thus, inhibition of spontaneous apoptosis of leukemic cells mediated by phosphorylation of AKT/Bcl-2 pathway results in protection of leukemic cells by BMSCs, which decreases after BMSCs exposure to chemotherapy. Targeting both the tumor cells and intervening in their interaction with the bone marrow microenvironment may thus affect clinical outcome in AML.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1029-2403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
134-48
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Chemotherapeutic treatment of bone marrow stromal cells strongly affects their protective effect on acute myeloid leukemia cell survival.
pubmed:affiliation
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article