[Clinical significance of multidrug resistance in acute leukemias].
A significant number of patients with acute leukaemias fail in their treatment as a result of the development of resistance to chemotherapy. Several evidences indicate that the expression of a mdr 1 gen, which codifies for P glycoprotein (PgP), contributes to this resistance in leukaemic cells. PgP functions as an energy-dependent efflux pump transporting a variety of unrelated drugs to the outside of the cells. It is possible to modulate this efflux using a number of drugs known as multidrug resistance (MDR) reversors or modulating agents. The present paper discusses some of the methods used for detecting the MDR phenotype, although the most reliable results are the ones that take into account an association of various methods. Despite the existence of disagreements regarding which method presents the greatest sensitivity or specificity the majority of authors agrees that the MDR phenotype, in isolation, affects the prognosis of leukaemias. The, coexpression of PgP with the molecule CD34 confers the worst prognosis in acute leukaemias. The authors demonstrate using cell cultures testing chemotherapeutic agents, alone or associated to modulating agents, that this line of research may allow in the future to elaborate an individualized clinical treatment. They emphasize the necessity of integration between haematologists and basic research as this may lead to a new therapeutic option for refractory patients to conventional treatment.
Maia
R C
RC
Centro de Pesquisa Básica, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro.
Rumjanek
V M
VM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001773:Blood Cells / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology / Q000627:therapeutic use; D007223:Infant; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011379:Prognosis; D012008:Recurrence; D012235:Rhodamines / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012235:Rhodamines; D016572:Cyclosporine; D014700:Verapamil; D015255:Idarubicin