Carboplatin‐Induced Thrombocytopenia through JAK2 Downregulation, S‐Phase Cell Cycle Arrest, and Apoptosis in Megakaryocytes

Chemotherapy‐induced thrombocytopenia (CIT) is a common complication when treating malignancies with cytotoxic agents wherein carboplatin is one of the most typical agents causing CIT. Janus kinase 2 (JAK2) is one of the critical enzymes to megakaryocyte proliferation and differ-entiation. However, the role of the JAK2 in CIT remains unclear. In this study, we used both car-boplatin‐induced CIT mice and MEG‐01 cell line to examine the expression of JAK2 and signal trans-ducer and activator of transcription 3 (STAT3) pathway. Under CIT, the expression of JAK2 was significantly reduced in vivo and in vitro. More surprisingly, the JAK2/STAT3 pathway remained inactivated even when thrombopoietin (TPO) was administered. On the other hand, carboplatin could cause prominent S phase cell cycle arrest and markedly increased apoptosis in MEG‐01 cells. These results showed that the thrombopoiesis might be interfered through the downregulation of JAK2/STAT3 pathway by carboplatin in CIT, and the fact that exogenous TPO supplement cannot reactivate this pathway.