Bone marrow stem cell protection from chemotherapy by low--molecular-weight compounds.
The stem cells of the bone marrow have the capacity for both self-renewal and derivation of all the blood cell lineages. Consequently, toxicity to these cells can result in neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, or aplastic anemia. Many anticancer drugs adversely affect the bone marrow, and neutropenia is a common limiting factor in dose escalation. In this review, we discuss agents that appear to have potential as bone marrow sparing agents. Computerized catalogs of the National Library of Medicine and Medline were searched for reports on low-molecular-weight compounds that detailed effects on the hematopoietic progenitor cells. The most promising agents are the endogenous peptides p-glutamic acid-glutamic acid-aspartic acid-cysteine-lysine and acetyl-serine-aspartic acid-lysine-proline, and the exogenous compounds amifostine and ammonium trichloro[dioxoethylene-O,O']tellurate, but several others are also discussed. These compounds preserve stem cell function in the presence of antineoplastic drugs of diverse pharmacological classes, and they do so by various mechanisms of action. Their present status in clinical practice is also detailed. More needs to be learned about their mechanisms of action and therapeutic potential, but the results are encouraging for some of these compounds and more clinical trials should be expected.
Guest
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I
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Uetrecht
J
J
D004999:Amifostine / Q000627:therapeutic use; D000741:Anemia, Aplastic / Q000139:chemically induced / Q000517:prevention & control; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001854:Bone Marrow Cells / Q000187:drug effects*; D005030:Ethylenes / Q000627:therapeutic use; D006131:Growth Inhibitors / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control; D016239:MEDLINE; D008970:Molecular Weight; D009842:Oligopeptides / Q000627:therapeutic use; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
D000970:Antineoplastic Agents; D005030:Ethylenes; D006131:Growth Inhibitors; D009842:Oligopeptides; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate; C040758:hemoregulatory peptide 5b; C058504:goralatide; D004999:Amifostine; D011761:Pyrrolidonecarboxylic Acid