Semiquantitative RT-PCR evaluation of the MDR1 gene expression in patients with acute myeloid leukemia
Abstract:
Resistance to chemotherapy is one of the major obstacles to effective treatment in acute myeloid leukemia (AML). The most extensively studied protein involved in multidrug resistance (MDR) is the transmembrane glycoprotein P (P-gp), the product of the multidrug resistance gene 1 (MDR1). MDR1/P-gp overexpression is frequently observed in hematological malignancies, especially in acute leukemia, and has been reported to correlate with poor prognosis in acute myeloid leukemia (AML). The aim of this study was to evaluate the level of MDR1 gene expression in bone marrow and/or peripheral blood samples in 92 AML patients in relation to their prognosis. The analyzed group was stratified according to presence or absence of prognostically favorable aberrations (PFAs), such as t(15;17) with PML/RARα fusion gene, t(8;21) with AML1/ETO fusion gene or inv(16)/ t(16;16) with CBFβ/MYH11 fusion gene. These prognostically favorable aberrations were detected by RT-PCR and/or standard cytogenetic techniques. MDR1 expression was detected by semiquantitative comparative RT-PCR using software-based evaluation. The levels of MDR1 expression in the bone marrow predicted induction of complete remission in the whole group of analyzed patients (P = 0.032). They were significantly lower in PFA negative patients who achieved complete remission compared to those who failed to achieve complete remission (P = 0.008). In PFA negative patients, MDR1 expression was higher when compared to PFA positive patients (P = 0.055). No such difference was found when analyzing peripheral blood samples. Our experiments showed no impact of MDR1 expression in bone marrow or peripheral blood cells on overall survival (P = 1.000 and P = 0.903 respectively). In summary, the present study shows the prognostic impact of MDR1 expression on induction of complete remission in AML patients. We confirmed that MDR1 overexpression is an unfavorable prognostic factor in AML, which may help to stratify the risk rate of PFA negative patients. In future studies, quantitative detection of MDR1 expression might be a valuable tool to predict prognosis in this patient subset.