Novel phosphatase-based regulatory loop for HbF expression

In this issue of Blood, Traxler et al1 using a novel CRISPR-Cas12a–based screening platform, have identified protein threonine phosphatase A (PTPA)–PP2A phosphatases as novel upstream mediator of BCL11A regulating fetal hemoglobin expression. In the last 2 decades, great efforts have been made in identifying pharmacologic inducers of fetal hemoglobin (HbF) production as therapeutic strategy for patients with either sickle cell disease (SCD) or transfusion dependent thalassemia (TDT).2,3 A very recent outcome of these efforts has been the approval of cell therapies targeting BCL11A, the main regulators of HbF switching, which have resulted in curative values of HbF production for patients with either SCD or TDT.