Targeted therapies for high-risk acute myeloid leukemia.
Approximately half of children with acute myeloid leukemia (AML) can be cured with contemporary chemotherapy regimens; however, various forms of drug resistance pose considerable obstacles for curing the remaining patients. Recent advances in immunology, cytogenetics, and cellular and molecular biology have provided new insights into fundamental biological differences between leukemic myeloid blasts and their normal counterparts. This article focuses on new technologies involving: (1) antibody- or growth factor-mediated targeting of antigens or growth factor receptors found on AML blasts and restricted sub-groups of normal cells, (2) pharmacologic targeting of the pathologic t(15;17) translocation of acute promyelocytic leukemia with all-trans retinoic acid, (3) pharmacologic and immunologic targeting of mutant RAS oncogenes and related aberrant signaling in AML blasts, and (4) targeting of pathological signaling of the Bcr-Abl oncoprotein and c-kit tyrosine kinase in myeloid leukemias. These advances herald an exciting new era of AML-specific therapies.
Perentesis
J P
JP
Division of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis, Minnesota, USA.
Sievers
E L
EL
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D000208:Acute Disease; D000328:Adult; D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000187:drug effects / Q000276:immunology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D015195:Drug Design; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005544:Forecasting; D000079982:Gemtuzumab; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D000922:Immunotoxins / Q000627:therapeutic use; D007223:Infant; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors / Q000235:genetics; D012306:Risk; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D018528:ATP-Binding Cassette Transporters; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D000922:Immunotoxins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D000079982:Gemtuzumab