Inhibitors of haemopoiesis and their potential clinical relevance

Current cytotoxic treatment regimens are most frequently dose-limited by the problem of myelotoxicity, and this could theoretically be prevented or reduced by the use of stem-cell inhibitors, since protection of this compartment during treatment could result in a more favourable outcome in terms of bone-marrow regeneration. Several negative stem-cell regulators have been identified, including macrophage inflammatory protein-1 alpha, transforming growth factor-beta, tumour necrosis factor-alpha, tetrapeptide and pentapeptide. All of these molecules have been shown to inhibit the proliferation of normal haemopoietic progenitors in bone marrow, and stem-cell protection from cytotoxic agents both in vitro and in vivo has been demonstrated. The potential use of inhibitors for the purging of tumour cells from stem-cell grafts is suggested by the observation that there is a differential response between normal and leukaemic progenitors to some inhibitors.