The effects of anagrelide on human megakaryocytopoiesis

Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens...

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Bibliographic Details
Published inBritish journal of haematology Vol. 99; no. 1; pp. 174 - 180
Main Authors Solberg Jr, Lawrence A., Tefferi, Ayalew, Oles, Karl J., Tarach, Jerzy S., Petitt, Robert M., Forstrom, Lee A., Silverstein, Murray N.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Science Ltd 01.10.1997
Blackwell
Subjects
Adult
Biological and medical sciences
Blood Platelets - cytology
Blood Platelets - drug effects
Blood. Blood coagulation. Reticuloendothelial system
Cell Division
Cell Survival
Cells, Cultured
Cellular Senescence - drug effects
digital imaging analysis
Female
glycoprotein IIb/IIIa
haemopoiesis
Humans
Male
Medical sciences
megakaryocyte
Megakaryocytes - cytology
Megakaryocytes - drug effects
Middle Aged
Pharmacology. Drug treatments
Platelet Aggregation Inhibitors - pharmacology
Quinazolines - pharmacology
Stem Cells
Human
Megakaryocytopoiesis
Hematopoiesis
Stem cell
Hematopoietic cell
Megakaryocyte
Digital image
Cell differentiation
Mechanism of action
Antiplatelet agent
Anagrelide
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Summary:Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic‐committed progenitor cells (CFU‐M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU‐M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU‐M in vitro. In‐vivo and in‐vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0007-1048
1365-2141
DOI:10.1046/j.1365-2141.1997.3503164.x