Authors: Michael Fiegl Inka Zimmermann Isolde Lorenz Wolfgang Hiddemann Jan Braess
Publish Date: 2007/08/21
Volume: 87, Issue: 1, Pages: 27-33
Abstract
Only about one third of all patients with acute myeloid leukemia AML will be cured by common chemotherapy regimens Susceptibility towards chemotherapy either of the leukemic bulk or the leukemic stem cell is considered the major determining parameter for longterm outcome The purpose of the present study was to investigate whether chemoresistance was correlated between different antileukemic drugs or not We determined the lethal concentration of chemotherapy necessary to reduce viability of cells to 50 compared to untreated control LC50 as a surrogate marker of chemotherapy susceptibility of six established chemotherapeutic agents cytarabine median 083 μg/ml daunorubicine 009 μg/ml idarubicine 003 μg/ml mitoxantrone 005 μg/ml etoposide 481 μg/ml and topotecan 014 μg/ml in an overall number of 147 samples from consecutive patients with AML by WST1 assay in vitro We found that susceptibility to chemotherapy was significantly correlated between all six agents all p values 001 A homogenous response of the blast populations was significantly correlated to high chemoresistance These data indicate that crossresistance in AML against antileukemic drugs exists between agents with different modes of action and seems not to be mediated by drugspecific resistance mechanisms but rather by more generalized deathdefying features of the affected cells eg inhibited apoptosis
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