Thrombopoietin (THPO) has been well characterized as a key regulator of platelet production. THPO also plays an important role in the maintenance and regulation of hematopoietic stem cells (HSCs). In this issue of EMBO Molecular Medicine, Pecci et al () describe a newly identified homozygous mutation in THPO causing congenital amegakaryocytic thrombocytopenia, a disease characterized by a significant impairment in platelet production with rapid onset of aplastic anemia within a few years. The paper nicely investigates the underlying pathogenic mechanisms of this disease. Importantly, this study, in tandem with other recent ones, shows that this rare genetic form of aplastic anemia is treatable with THPO receptor agonists, emphasizing the paramount role of genetic testing in cases of aplastic anemia and other bone marrow failure disorders. This report also refines our understanding of the role of THPO in human HSC function and illustrates the important biological insight that can be gained through studies of such rare genetic disorders.
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