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Blood transcriptome and clonal T cell correlates of response and nonresponse to eltrombopag therapy in a cohort of patients with chronic immune thrombocytopenia

ABSTRACT: We evaluated the longitudinal effect of eltrombopag, a thrombopoietin receptor agonist, on gene expression in heavily pretreated patients with chronic immune thrombocytopenia (ITP) using blood transcriptome analysis on pretreatment, and following 1 week and 1 month of treatment samples. A strong stimulation of 208 eltrombopag-induced genes was identified in responders at 1-week time point. 90% of these genes are present in platelets, with GATA1, THPO, VIPAS39 and TGFB1 as top upstream regulators. Subsequently, despite a continued increase in platelet in responders, the eltrombopag-induced gene expression decreased at 1 month compared with the level at 1-week time point. This novel observation of the longitudinal effect of eltrombopag therapy over time suggests different stages of eltrombopag response. Non-responders did not exhibit eltrombopag-induced gene expression changes. This study provides novel insights into the mechanisms of eltrombopag response and nonresponse.

ORGANISM(S): Homo sapiens

PROVIDER: GSE112278 | GEO | 2021/03/21

REPOSITORIES: GEO

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