Functional analysis of P-glycoprotein and multidrug resistance associated protein related multidrug resistance in AML-blasts.

Abstract:

:Despite the high effectiveness of various P-glycoprotein (P-gp) modulating substances in vitro their clinical value e.g. for combination treatment of acute myelogenous leukemias (AML) remains still unclear. This might be explainable by recent findings that other factors than P-gp (e.g. the multidrug resistance associated protein (MRP)) may also be involved in clinical occurring drug resistance. To study P-gp and MRP mediated MDR in AML blasts from patients with relapses at the functional level we measured rhodamine 123 (RHO) efflux in combination with a P-gp specific (SDZ PSC 833) or a MRP specific (MK571) modulator, respectively. Furthermore, direct antineoplastic drug action was monitored by determination of damaged cell fraction of a blast population using flow cytometry. We generally found strongly modulated RHO efflux by SDZ PSC 833 but slight RHO-efflux modulation by MK571 in blasts from relapsed states of AML expressing MDR1 or MRP mRNA at various levels. We could not demonstrate, though, significant PSC 833 or MK571 mediated modulation of the cytotoxic effects of etoposide. The results point to the possibility that combination of etoposide and a modulator might not improve responses to chemotherapy by targeting P-gp or MRP exclusively.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Brügger D,Herbart H,Gekeler V,Seitz G,Liu C,Klingebiel T,Orlikowsky T,Einsele H,Denzlinger C,Bader P,Niethammer D,Beck JF

doi

10.1016/s0145-2126(98)00192-1

keywords:

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

467-75

issue

5

eissn

0145-2126

issn

1873-5835

pii

S0145212698001921

journal_volume

23

pub_type

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