Abstract
One of the major problems in the treatment of leukemia is the development of drug resistance to chemotherapeutic agents, which is already present at diagnosis or after chemotherapy as a minimal residual disease. The resistance may be originated from genetic or epigenetic mutations during prior growth of the leukemic clone. In this study, the expressions of three multidrug resistance (MDR) genes were investigated. Expression levels of multidrug resistance resistance gene 1 (MDR1), breast cancer resistance protein (BCRP) gene, and lung resistance protein (LRP) gene expression levels were determined in peripheral blood samples from 16 cases of chronic lymphocytic leukemia (CLL) and from 23 cases of chronic myelogeneous leukemia (CML) using RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to β2-microglobulin gene expression in densitometric measurements. MDR1, BCRP and LRP expression levels was detected in 56,3%, 18,8% and 50% of CLL patients, respectively, with no difference for stage or response to the treatment. Four out of 16 (25%) CLL patients expressed none of these genes. The other 25% CLL patients expressed all of these genes. MDR1, BCRP and LRP expression was detected in 47,8%, 39,1% and 30,4% of CML patients, respectively, with no difference for progression or response to imatinib mesylate. Eight out of 23 (34,8%) CML patients expressed none of these genes. Four out of 23 (17,4%) CML patients expressed all of these genes, and two out of whom rapidly progressed to acute leukemia and unresponsive to the treatment. In conclusion, MDR and LRP overexpression seems to be a frequent event in CLL and CML patients; however no conclusion can be drawn on their prognostic role and response to the treatment.
Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression
