Impact of Hydroxycarbamide Treatment on the Whole Blood Transcriptome in Sickle Cell Disease

Hydroxycarbamide (HC, also known as hydroxyurea) is the most widely used therapeutic for individuals with sickle cell disease (SCD). HC's clinical benefits are primarily associated with its ability to induce fetal hemoglobin (HbF). However, much remains unknown about the non-HbF related impact of HC on genes and pathways relevant to SCD pathophysiology. In this study, we performed bulk RNA-Seq on whole blood samples collected from a cohort of 25 pediatric patients with SCD to identify genes and pathways that are affected by treatment with HC. The results illustrate the range of effects exerted by HC during therapy for SCD and pave the way for an improved understanding of the HbF induction-independent benefits of HC. Overall design: Whole blood samples were collected at pre-HC (pre-HU) and at the maximum tolerated dose of HC (HU MTD). Gene expression profiling was performed with RNA-Seq.