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 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.
Solberg
L A
LA
Division of Hematology/Oncology, Mayo Clinic Jacksonville, Florida 32224, U.S.A.
Tefferi
A
A
Oles
K J
KJ
Tarach
J S
JS
Petitt
R M
RM
Forstrom
L A
LA
Silverstein
M N
MN
D000328:Adult; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D013234:Stem Cells
D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C021139:anagrelide