P-glycoprotein in primary acute myeloid leukemia and treatment outcome of idarubicin/cytosine arabinoside-based induction therapy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-06

AUTHORS

HJ Broxterman, P Sonneveld, WJL van Putten, J Lankelma, CA Eekman, GJ Ossenkoppele, HM Pinedo, B Löwenberg, GJ Schuurhuis

ABSTRACT

The expression of the drug transport protein, P-glycoprotein (Pgp/MDR1) has been found to be of prognostic significance for the achievement of complete remission (CR) or the duration of survival after daunorubicin (DNR)-containing induction therapy in acute myeloid leukemia (AML). This would suggest that the expression of Pgp in AML is high enough to have significant impact on intracellular DNR concentrations and on clinical therapy failure in AML. Recently, DNR has been replaced in many centers by idarubicin (IDA) as the first choice anthracycline in AML treatment. We have, therefore, performed a study in a group of 98 primary AML patients, who all received IDA, but not DNR during induction therapy in order to determine if the response to IDA-containing induction therapy might be related to the biologic characteristic of Pgp expression in AML. The AML samples were studied for Pgp expression by MRK16 antibody staining and for Pgp activity measured as the modulation of rhodamine 123 uptake by 2 microM PSC 833. No correlation of Pgp with complete response rate, event-free survival or overall survival was found. In addition to Pgp, the expression of another protein that has been implicated by some studies in response failure to DNR-containing therapy, the major vault protein (Mvp/LRP), was studied. This marker did not correlate with CR or survival after IDA-containing therapy. The results of this patient study are consistent with model studies showing that the steady-state cellular accumulation of lipophilic anthracyclines such as IDA are little affected by Pgp. Therefore, putative beneficial effects of the inclusion of PSC 833 in IDA-containing therapy might rather be related to alternative mechanisms than to inhibition of Pgp-mediated IDA efflux. More... »

PAGES

2401796

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.leu.2401796

DOI

http://dx.doi.org/10.1038/sj.leu.2401796

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036122937

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10865967


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/sj.leu.2401796'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/sj.leu.2401796'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.leu.2401796'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.leu.2401796'


 

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