Novel role of STAT1 in the recovery from doxorubicin induced immuno‐suppression

Abstract

Signal Transducer and Activator of Transcription 1 (STAT1) is known to play a role in sensitizing cells to chemotherapy induced apoptosis. Doxorubicin (Dox), a commonly used chemotherapeutic drug is known to exert serious side effects, most remarkably cardiotoxicity and myelosuppression. In this study we analyzed the role of STAT1 in Dox induced toxicity and recovery using STAT1 knock out (KO) mice. Dox injected STAT1 wild type (WT) mice showed an early onset of acute toxicity whereas toxicity in KOmice was later but prolonged. A strong effect of Dox on the organs related to immune function such as shrinkage of spleen and thymus were only observed in KO mice on day 16 after Dox injection. Flow‐cytometry analysis of peripheral blood cells from KO mice showed an increase in the granulocyte population but a decrease in B lymphocytes, while no change was noted in WT mice. A severe depletion of bone marrow cellularity was observed on day 3 in both WT and KO mice. However, after 16 days WT mice were able to partially restore the depleted bone marrow, while KO mice were recovering more slowly. On day 30, WT mice showed significant recovery on the population of bone marrow progenitors and B lymphocytes compared to a little recovery in the KO mice. In summary, STAT1 KO mice are differentially sensitive to Dox induced lympho‐toxicity, thus STAT1 has an important role in the recovery from Dox induced immuno‐suppression. Supported by IFTZ grant (WD).