Haemoprotection against cytostatic drugs by stem cell inhibition.
Cytostatic drug-induced haematopoietic damage is a major problem in tumour chemotherapy, due to the intensive proliferation of many bone marrow constituents and to the drug-induced recruitment of immature pluripotent haematopoietic cells (spleen colony-forming units, CFU-S). Marie-Hélène Moser and Walter Paukovits discuss how it should be possible to minimize such proliferation-associated damage by inhibiting CFU-S during the most dangerous treatment phases, with factors such as transforming growth factor beta, tumour necrosis factor alpha, macrophage inflammatory protein 1 alpha, and the CFU-S-inhibitory peptides N-acetyl-Ser-Asp-Lys-Pro and pyroGlu-Glu-Asp-Cys-Lys (pEEDCK). Clinically relevant data are available for pEEDCK, showing that application of this peptide leads to a delayed, shorter, and less severe neutropenia, combination of pEEDCK with a stimulator avoids neutropenia, and stem cell preservation with pEEDCK improves long-term reconstitution of the haematopoietic system. Stem cell inhibition by synthetic peptides like pEEDCK may provide a useful strategy for bone marrow protection.
Moser
M H
MH
Laboratory of Growth Regulation, University of Vienna, Austria.
Paukovits
W R
WR
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D006402:Hematologic Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans
D000970:Antineoplastic Agents