New developments in the treatment of acute myeloid leukemia.
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.
Smeets
M
M
University Hospital St. Radboud, Nijmegen, The Netherlands.
de Witte
T
T
van der Lely
N
N
Raymakers
R
R
Muus
P
P
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D003115:Colony-Stimulating Factors; D003561:Cytarabine