Imatinib mesylate inhibits autonomous erythropoiesis in patients with polycythemia vera in vitro.
The overproduction of red blood cells in patients with polycythemia vera (PV) is reflected in vitro by the formation of erythroid burst-forming units (BFU-Es) in the absence of exogenous erythropoietin. In contrast to other myeloproliferative disorders, the molecular mechanism of PV is unknown and no specific chromosomal abnormality has been described. We speculated that imatinib mesylate may reverse the pathological overproduction of red cells by inhibition of autonomous erythropoiesis. In the present study, imatinib mesylate was found to either block or strongly inhibit autonomous BFU-E formation in vitro in all patients tested. Moreover, autonomous BFU-E growth was also markedly reduced by exposure of PV cells to imatinib mesylate prior to cultivation in semisolid medium. The profound effect of imatinib mesylate on autonomous erythropoiesis suggests the involvement of an as yet unidentified kinase in the pathogenesis of PV and should provide the rationale for a forthcoming clinical trial.
Oehler
Leopold
L
Internal Medicine I, Division of Hematology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. leopold.oehler@akh-wien.ac.at
Jaeger
Eva
E
Eser
Alexander
A
Sillaber
Christian
C
Gisslinger
Heinz
H
Geissler
Klaus
K
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D066298:In Vitro Techniques; D010879:Piperazines / Q000008:administration & dosage*; D011087:Polycythemia Vera / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate