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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2000-11-27
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pubmed:abstractText |
Despite treatment with intensive chemotherapy, a considerable number of patients with acute myeloid leukemia (AML) die from their disease due to the occurrence of resistance. Overexpression of the transporter proteins P-glycoprotein (P-gp) and multidrug resistance protein (MRP) 1 has been identified as a major cause of cross-resistance to functionally and structurally unrelated drugs. In the present study, the functional activity of P-gp and MRP was determined in 104 de novo AML patients with a flow cytometric assay using rhodamine 123 (Rh123) in combination with PSC833 and carboxyfluorescein (CF) in combination with MK-571. The results were compared with clinical outcome and with known prognostic factors. The functional activity of P-gp and MRP, expressed as Rh123 efflux blocking by PSC833 and CF efflux blocking by MK-571, demonstrated a great variability in the AML patients. A strong negative correlation was observed between Rh123 efflux blocking by PSC833 and Rh123 accumulation (r(s) = -0.69, P < 0.001) and between CF efflux blocking by MK-571 and CF accumulation (r(s) = -0.59, P < 0.001). A low Rh123 accumulation and a high Rh123 efflux blocking by PSC833 were associated with a low complete remission (CR) rate after the first cycle of chemotherapy (P = 0.008 and P = 0.01, respectively). Patients with both low Rh123 and CF accumulation (n = 16) had the lowest CR rate (6%), whereas patients with both high Rh123 and CF accumulation (n = 11) had a CR rate of 73%. AML patients with French-American-British classification M1 or M2 showed a lower Rh123 accumulation than patients with French-American-British classification M4 or M5 (P = 0.02). No association was observed between the multidrug resistance parameters and overall survival of the AML patients. Risk group was the only predictive parameter for overall survival (P = 0.003).
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/6-carboxyfluorescein,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluoresceins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Propionates,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Rhodamine 123,
http://linkedlifedata.com/resource/pubmed/chemical/valspodar,
http://linkedlifedata.com/resource/pubmed/chemical/verlukast
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1078-0432
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3205-14
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10955805-ATP-Binding Cassette Transporters,
pubmed-meshheading:10955805-Adolescent,
pubmed-meshheading:10955805-Adult,
pubmed-meshheading:10955805-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:10955805-Cyclosporins,
pubmed-meshheading:10955805-Drug Resistance, Multiple,
pubmed-meshheading:10955805-Drug Resistance, Neoplasm,
pubmed-meshheading:10955805-Female,
pubmed-meshheading:10955805-Flow Cytometry,
pubmed-meshheading:10955805-Fluoresceins,
pubmed-meshheading:10955805-Fluorescent Dyes,
pubmed-meshheading:10955805-Glutathione,
pubmed-meshheading:10955805-Humans,
pubmed-meshheading:10955805-Leukemia, Myeloid,
pubmed-meshheading:10955805-Male,
pubmed-meshheading:10955805-Middle Aged,
pubmed-meshheading:10955805-Multidrug Resistance-Associated Proteins,
pubmed-meshheading:10955805-Neoplasm Proteins,
pubmed-meshheading:10955805-P-Glycoprotein,
pubmed-meshheading:10955805-Propionates,
pubmed-meshheading:10955805-Quinolines,
pubmed-meshheading:10955805-RNA, Messenger,
pubmed-meshheading:10955805-Randomized Controlled Trials as Topic,
pubmed-meshheading:10955805-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10955805-Rhodamine 123,
pubmed-meshheading:10955805-Survival Analysis,
pubmed-meshheading:10955805-Treatment Outcome,
pubmed-meshheading:10955805-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
P-glycoprotein and multidrug resistance protein activities in relation to treatment outcome in acute myeloid leukemia.
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pubmed:affiliation |
Department of Hematology, University Hospital Groningen, the Netherlands.
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pubmed:publicationType |
Journal Article
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