Effects of cytarabine and various anthracyclins on platelet activation: characterization of in vitro effects and their possible clinical relevance in acute myelogenous leukemia.
Previous in vitro studies have demonstrated that normal platelets and platelet-released mediators can alter in vitro characteristics of human acute myelogenous leukemia (AML) blasts. To further investigate whether platelets can be expected to adhere to and thereby affect AML blasts through their release of soluble mediators into a common microenvironment, we investigated (i) the effects on platelet activation by cytotoxic drugs commonly used in AML therapy; (ii) the occurrence of circulating activated platelets in acute leukemia patients; and (iii) the in vivo and in vitro adherence of platelets to AML blasts. The anthracyclins daunorubicin and idarubicin increased the expression of activation-associated membrane molecules (GPIIb/IIIa, CD62P, CD63) by normal platelets, daunorubicin then having the strongest effect. In contrast, cytarabine, epirubicin, doxorubicin and mitoxantrone had no significant effects. Although AML patients did not show increased levels of activated platelets in the circulation, adhesion of platelets to AML blasts was demonstrated both in vivo and in vitro. These results suggest that platelets and AML blasts may locate to common in vivo microenvironments, and platelet-derived soluble mediators may thereby affect the functional characteristics of the leukemia cells.
Foss
Brynjar
B
Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway.
Ulvestad
Elling
E
Hervig
Tor
T
Bruserud
Øystein
Ø
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D060149:Tetraspanin 30; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; C554586:CD63 protein, human; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D003561:Cytarabine