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Five putative drug resistance parameters (MDR1/P‐glycoprotein, MDR‐associated protein, glutathione‐S‐transferase, bcl‐2 and topoisomerase IIα) in 57 newly diagnosed acute myeloid leukaemias
Author(s) -
Lohri Andreas,
Hille Benoît,
Bacchi Marisa,
Fopp Markus,
Joncourt Franzisca,
Reuter Jürgen,
Cerny Thomas,
Fey Martin F.,
Herrmann Richard
Publication year - 1997
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1997.tb00979.x
Subject(s) - topoisomerase , p glycoprotein , drug resistance , glutathione transferase , myeloid , glutathione , pharmacology , cancer research , glutathione s transferase , drug , myeloid leukemia , multiple drug resistance , medicine , biology , enzyme , biochemistry , genetics
Using a modified quantitative reverse transcriptase (RT) PCR assay in 57 patients with acute myeloid leukaemia (AML) from a Swiss Phase III multicentre study (SAKK 30/85), we measured the m‐RNA expression of the genes from the multidrug resistance gene 1 (MDR1), the multidrug resistance associated protein (MRP), glutathione‐S‐transferase (GST) π, bcl‐2 and topoisomerase (topo) IIα. P‐glycoprotein (p‐gp) was measured by Western blot, and GST activity by functional assays. To analyse progression‐free (PFS) and overall survival (OS), parameters were prospectively divided into “low” and “high” groups, according to their median values (exceptions: MDR1 and p‐gp). Median follow‐up was 60 months. Results: MDR1‐ and MRP mRNA levels correlated with each other ( r = 0.54, Spearman), FABM4/M5 and extramedullary disease. “Low” bcl‐2‐mRNA predicted longer PFS: 22 months vs. 7 months (median, p = 0.02, log rank), and longer OS: 64 months vs. 14 months ( p = 0.06). “Low” topo Hoc predicted poorer outcome: median PFS 9 vs. 19 months ( p = 0.03); median survival 12 months vs. “not reached” ( p = 0.03). An improved outcome tendency, albeit nonsignificant, was seen in p‐gp‐negative patients. In a Cox model adjusted for age, performance status, presence of Auer rods, FAB type and clinical response, bcl‐2 and topo IIα mRNA levels retained their predictive values.