The Development of Cytokine Receptor Antagonists as Potential Therapeutic Agents for the Myeloproliferative Disorders

The aetiology of the myeloproliferative disorders and, in particular, of the myeloid leukaemias is unknown. The transformation of cells is primarily due to molecular aberrations leading to excessive cellular signalling and proliferation. In addition cytokines and their receptors may play a role in leukaemogenesis by increasing the proliferative capacity of leukaemic cells and extending their life span. Chemotherapeutic agents are regularly used to treat patients with leukaemia but they are nondiscriminatory treatments that kill both healthy and cancer cells. Consequently patients receiving chemotherapy suffer unwanted toxicities in both the haematological and other systems. Therapies that specifically target malignant cells sparing normal cells are being investigated in a number of contexts. Cytokine antagonists can target growth factor-dependent cells by obstructing the interaction between cytokine and receptor. In this review we will discuss the myeloproliferative disorders in particular the leukaemias, the cytokines involved in leukaemogenesis, and the therapeutic potential of new agents that block specific cytokines.