Inhibitors of haemopoiesis and their potential clinical relevance

Blood Rev. 1995 Dec;9(4):226-33. doi: 10.1016/s0268-960x(95)90014-4.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Chemokine CCL4
  • Drug Evaluation, Preclinical
  • Growth Inhibitors / pharmacology*
  • Hematopoiesis / drug effects*
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Macrophage Inflammatory Proteins / pharmacology
  • Molecular Sequence Data
  • Transforming Growth Factor beta / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Chemokine CCL4
  • Growth Inhibitors
  • Macrophage Inflammatory Proteins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha