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.
Parker
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AN
Beatson Institute for Cancer Research, Glasgow, UK.
Pragnell
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IB
D000595:Amino Acid Sequence; D054407:Chemokine CCL4; D004353:Drug Evaluation, Preclinical; D006131:Growth Inhibitors / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008969:Molecular Sequence Data; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D054407:Chemokine CCL4; D006131:Growth Inhibitors; D019402:Macrophage Inflammatory Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha