title: New developments in the treatment of acute myeloid leukemia.
abstract: Remission induction therapy fails in 20-30% of the patients with acute myeloid leukemia (AML) despite dose intensification and the use of new and more effective drugs. Primary and acquired drug resistance, metabolic or kinetic are a fundamental problem. Expression of the P-glycoprotein in AML is correlated with therapeutic outcome. Randomized clinical studies with Pgp modulators are currently on-going. Ara-C and anthracyclines, are preferentially cytotoxic to proliferating cells. Proliferation induction of leukemia blasts with growth factors in vitro resulted in an increased toxicity of Ara-C and anthracyclines. Normal hematopoietic blast cells with a high Pgp expression are noncycling and less sensitive to anthracyclines, in contrast to the more proliferating cells with a low Pgp expression. Proliferation induction by growth factors results in a down regulation of Pgp expression. Priming of leukemic cells with growth factors in vivo might be promising and randomized clinical studies are warranted.
authors.affiliation: University Hospital St. Radboud, Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Smeets
authors.forename: T
authors.initials: T
authors.lastname: de Witte
authors.forename: N
authors.initials: N
authors.lastname: van der Lely
authors.forename: R
authors.initials: R
authors.lastname: Raymakers
authors.forename: P
authors.initials: P
authors.lastname: Muus
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003115:Colony-Stimulating Factors / Q000502:physiology / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D012074:Remission Induction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D003115:Colony-Stimulating Factors; D003561:Cytarabine