Recombinant human tyrosyl-tRNA synthetase, a novel thrombopoietic agent.

Chemo- and radiotherapy induced thrombocytopenia present significant limitations for tumor therapy. In this study, we examined the therapeutic effect of recombinant human tyrosyl-tRNA synthetase (rhTyrRS) against development of thrombocytopenia in cyclophosphamide (CTX) treated mice. Our data indicate that intraperitoneal administration of at least 10 μg/day rhTyrRS for 7 days significantly prevents the decrease in platelets 8 days after CTX injection. The data further demonstrate that rhTyrRS promotes migration and aggregation of megakaryocytes to the bone marrow niche. Real-time PCR and flow cytometry reveal that VCAM-1 is particularly important for the adhesion. Together, these data suggest that rhTyrRS might be a useful therapeutic agent for chemotherapy-induced thrombocytopenia.