Bone marrow stem cell protection from chemotherapy by low--molecular-weight compounds. 2001

I Guest, and J Uetrecht
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.

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.

UI MeSH Term Description Entries
D007970 Leukopenia A decrease in the number of LEUKOCYTES in a blood sample below the normal range (LEUKOCYTE COUNT less than 4000). Leukocytopenia,Leukocytopenias,Leukopenias
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D011761 Pyrrolidonecarboxylic Acid A cyclized derivative of L-GLUTAMIC ACID. Elevated blood levels may be associated with problems of GLUTAMINE or GLUTATHIONE metabolism. 5-Oxoproline,Pidolic Acid,Pyroglutamic Acid,5-Ketoproline,5-Oxopyrrolidine-2-Carboxylic Acid,Magnesium Pidolate,Pyroglutamate,Pidolate, Magnesium
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D004999 Amifostine A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. Ethiofos,Gammaphos,APAETP,Amifostine Anhydrous,Amifostine Disodium Salt,Amifostine Monohydrate,Amifostine Monohydrochloride,Amifostine Trihydrate,Aminopropyl Aminoethylthiophosphate,Aminopropylaminoethylthiophosphate,Aminopropylaminoethylthiophosphoric Acid,Ethanethiol, 2-((3-aminopropyl)amino)-, dihydrogen phosphate (ester), trihydrate,Ethiofos Anhydrous,Ethyol,NSC-296961,S-(N-(3-Aminopropyl)-2-aminoethyl)thiophosphoric Acid,WR-2721,YM-08310,NSC 296961,NSC296961,WR 2721,WR2721,YM 08310,YM08310
D005030 Ethylenes Derivatives of ethylene, a simple organic gas of biological origin with many industrial and biological use.
D006131 Growth Inhibitors Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth ( Cell Growth Inhibitor,Cell Growth Inhibitors,Growth Inhibitor,Growth Inhibitor, Cell,Growth Inhibitors, Cell,Inhibitor, Cell Growth,Inhibitor, Growth,Inhibitors, Cell Growth,Inhibitors, Growth
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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