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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-4-13
pubmed:abstractText
In vitro culture systems that parallel in vivo growth conditions are needed to study leukemia biology and to accurately test therapeutic efficacies. We investigated the effects of the HS-5 human bone marrow stromal cell line on cultured primary leukemia cell survival and chemosensitivity.A total of 30 bone marrow (BM) samples from untreated acute myeloid leukemia (AML) patients were cultured for 96 hours with serum and growth factors, without HS-5, or in direct contact with HS-5 monolayers, or with HS-5 separated from AML cells by transwell inserts. In some experiments, cytosine arabinoside or daunomycin was added for the last 18 hours of culture. Apoptosis frequencies, bcl-2 protein expression, proliferating cell nuclear antigen expression, and cell cycle distributions were determined in four-color flow cytometry analyses of CD45(+) leukemia cells. In comparison to control growth conditions, direct contact with HS-5 significantly inhibited culture-induced and drug-induced apoptosis of AML cells. Direct contact of AML cells with HS-5 significantly increased short-term proliferation and viability, and colony formation of primary AML cells. HS-5-mediated apoptosis inhibition was not consistently associated with increased bcl-2 protein in AML cells. Noncontact conditions inhibited drug-induced apoptosis significantly less than direct contact with HS-5. Coculture of AML cells on HS-5 monolayers improved in vitro leukemia cell survival and attenuated chemotherapy-induced leukemia cell killing. This has practical significance, increasing the fraction of primary AML samples that can be analyzed in vitro, and allows drug sensitivity testing in growth conditions more similar to the bone marrow microenvironment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0301-472X
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
448-57
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed-meshheading:11301185-Antigens, CD45, pubmed-meshheading:11301185-Antineoplastic Agents, pubmed-meshheading:11301185-Apoptosis, pubmed-meshheading:11301185-Bone Marrow Cells, pubmed-meshheading:11301185-Cell Cycle, pubmed-meshheading:11301185-Cell Division, pubmed-meshheading:11301185-Coculture Techniques, pubmed-meshheading:11301185-Colony-Forming Units Assay, pubmed-meshheading:11301185-Culture Media, Conditioned, pubmed-meshheading:11301185-Cytarabine, pubmed-meshheading:11301185-Daunorubicin, pubmed-meshheading:11301185-Flow Cytometry, pubmed-meshheading:11301185-Humans, pubmed-meshheading:11301185-Leukemia, Myeloid, Acute, pubmed-meshheading:11301185-Proliferating Cell Nuclear Antigen, pubmed-meshheading:11301185-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:11301185-Stromal Cells, pubmed-meshheading:11301185-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5).
pubmed:affiliation
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D-100, Seattle, WA 98109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't