TY - JOUR
T1 - Low incidence of MDR1 expression in acute promyelocytic leukaemia
AU - DRACH, DORIS
AU - ZHAO, SHOURONG
AU - DRACH, JOHANNES
AU - ANDREEFF, MICHAEL
PY - 1995/6
Y1 - 1995/6
N2 - Summary. The MDR1 gene product, P‐glycoprotein, functions as a transmembrane efflux pump for certain cytotoxic agents including anthracyclines. Based upon the clinical observation that patients with acute promyelocytic leukaemia (APL) respond favourably to anthracyclines, we hypothesized that APL cells may have low levels of MDR1 expression. We therefore investigated MDR1 expression in 10 patients with APL and compared results with those obtained in 18 patients with other subtypes of acute myelogenous leukaemia (AML). Prior to reverse transcriptase polymerase chain reaction with MDR1 specific primers, leukaemic cells were purified by fluorescence activated cell sorting to exclude normal haemopoietic cells, in particular lymphocytes, from the MDR1 analysis. In sorted APL cells, MDR1 expression was detected in only two of 10 patients, which was significantly different from findings in other AML subtypes (MDR1 expression in 14/18 patients; P<0.01). When unsorted specimens from APL patients were studied, five of six cases were MDR1 positive, whereas sorted APL cells were shown to express MDR1 mRNA in only one of these cases. MDR1 mRNA levels expressed as MDRl/beta‐2 microglobulin ratios were significantly lower in APL (0‐24 –0‐2, mean –SD) than in AML (0‐75 –0‐48; P<0.01). We conclude that low or absent expression of MDR1 in APL cells may contribute to the efficacy of anthracyclines in the treatment of APL.
AB - Summary. The MDR1 gene product, P‐glycoprotein, functions as a transmembrane efflux pump for certain cytotoxic agents including anthracyclines. Based upon the clinical observation that patients with acute promyelocytic leukaemia (APL) respond favourably to anthracyclines, we hypothesized that APL cells may have low levels of MDR1 expression. We therefore investigated MDR1 expression in 10 patients with APL and compared results with those obtained in 18 patients with other subtypes of acute myelogenous leukaemia (AML). Prior to reverse transcriptase polymerase chain reaction with MDR1 specific primers, leukaemic cells were purified by fluorescence activated cell sorting to exclude normal haemopoietic cells, in particular lymphocytes, from the MDR1 analysis. In sorted APL cells, MDR1 expression was detected in only two of 10 patients, which was significantly different from findings in other AML subtypes (MDR1 expression in 14/18 patients; P<0.01). When unsorted specimens from APL patients were studied, five of six cases were MDR1 positive, whereas sorted APL cells were shown to express MDR1 mRNA in only one of these cases. MDR1 mRNA levels expressed as MDRl/beta‐2 microglobulin ratios were significantly lower in APL (0‐24 –0‐2, mean –SD) than in AML (0‐75 –0‐48; P<0.01). We conclude that low or absent expression of MDR1 in APL cells may contribute to the efficacy of anthracyclines in the treatment of APL.
KW - CD34
KW - P‐glycoprotein
KW - acute myelogenous leukaemia
KW - acute promyelocytic leukaemia
KW - multidrug resistance
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U2 - 10.1111/j.1365-2141.1995.tb05161.x
DO - 10.1111/j.1365-2141.1995.tb05161.x
M3 - Article
C2 - 7794759
AN - SCOPUS:0029015340
SN - 0007-1048
VL - 90
SP - 369
EP - 374
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 2
ER -