Normal HematopoiesisSustained enhancement of OCTN1 transporter expression in association with hydroxyurea induced γ-globin expression in erythroid progenitors

•UTB and OCTN1 transporter expression is differentially regulated during erythroid differentiation.•UTB and OCTN1 expression in erythroid progenitor increases with hydroxyurea treatment concomitant with γ-globin expression.•Hydroxyurea-mediated induction of OCTN1 is correlated with increased γ-globin expression in erythroid cells.•OCTN1 may be critical in mediating γ-globin induction by hydroxyurea.

The clinical benefits of hydroxyurea (HU) treatment in patients with sickle cell disease (SCD) are due largely to increased γ-globin expression. However, mechanisms that control γ-globin expression by HU in erythroid progenitors are incompletely understood. Here, we investigated the role of two HU transporters, urea transporter B (UTB) and organic cation/carnitine transporter 1 (OCTN1), in this process. Endogenous expression of both transporters peaked toward the end of erythroid differentiation. However, unlike UTB, HU-induced OCTN1 expression correlated positively with γ-globin level and was sustained throughout the period of induction. These results highlight a potential major role for OCTN1 in promoting the efficacy of HU.