[Multidrug resistance induced by surexpression of the mdrl gene].

Drug resistance of some tumors and hematopoietic diseases is a major problem for clinicians. One of the mechanisms of resistance is called the multidrug resistance. Multidrug resistance is a cross-reactive resistance between molecules different in structure and activities. Multidrug resistance is characterized by an active drug efflux through the cell membrane with a decrease in drug cellular accumulation. This efflux out of the cell is due to a membrane glycoprotein called P-glycoprotein or P-gp 170 encoded by the mdr1 gene. In humans, high levels of mdr1 gene expression are observed in normal tissues as adrenal gland, colon and kidney. Tumors derived from these tissues are usually resistant to chemotherapy. By contrast to this intrinsic drug resistance, acquired drug resistance is defined by the mdr1 gene expression in tumors which relapse and become refractory to chemotherapy as acute lymphoïd and myeloïd leukemia, breast and ovarian cancers, non-Hodgkin lymphomas and multiple myeloma. When the clinical significance of multidrug resistance will be defined, identification of non-responders patients should lead to the use of therapeutic regimens including mdr reversing agents.