Immunophenotyping as a guide for targeted therapy.
Immunophenotyping of acute and chronic leukaemias has revealed many lineage- and differentiation-specific antigens. It has now become possible to classify leukaemias according to their unique antigenic expression pattern. Among many lineage- and differentiation-specific antigens, disease-specific antigens are increasingly recognized because of their specific prognostic or therapeutic relevance. Expression of the multidrug resistance proteins of the ABC transporter family is associated with a poor response to treatment and a grave clinical prognosis. Recently, attempts to reverse refractory disease by using P-glycoprotein inhibitors have been performed in acute myeloid leukaemia, so far without evidence of clinical benefit. Other new leads to use antigen expression as a way of designing tumour-specific therapy have resulted in imatinib and Flt3 inhibitors which target tyrosine kinases in the leukaemic cell. Clinical trials are underway to investigate the effect of these new agents. The development of an antibody-calicheamycin complex directed against the myeloid-specific antigen CD33 has shown clinical activity in patients with relapsed acute myeloid leukaemia. The further development of these approaches is discussed.
Department of Hematology, Erasmus MC, Room L407, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. p.sonneveld@erasmusc.nl
Pieter
P
Sonneveld
Rob
R
Pieters
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000235:genetics; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D063268:Sialic Acid Binding Ig-like Lectin 3; D051941:fms-Like Tyrosine Kinase 3
D018435:ATP Binding Cassette Transporter, Subfamily B; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; C571163:CD33 protein, human; D011518:Proto-Oncogene Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3