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.