Hemoglobin alpha-like subunit mu is expressed during ontogeny and is elevated in alpha thalassemia Open Access

• Hemoglobin subunit mu (HBM) is an alpha-like globin chain that is expressed during gestation at levels similar to embryonic globins

• HBM levels are elevated in some alpha thalassemia patients likely because of compensation and could serve as a diagnostic biomarker

The alpha globin gene cluster on chromosome 16 encodes alpha-like globins whose expression changes during development. HBM located in this cluster was considered a pseudogene until its transcript was discovered in 2005, but without a detectable protein product. Here, we provide the first detailed description of HBM-encoded globin at the protein level (hemoglobin mu chain, HBM) across different age groups using liquid chromatography coupled with tandem mass spectrometry. Using targeted analysis, we demonstrate that HBM protein is readily detectable in circulation with its levels falling with increasing gestational age. We also report the levels of HBM in relation to other hemoglobin chains in neonatal, pediatric and adult blood. Additionally, analysis of alpha thalassemia patient samples revealed that HBM levels were elevated 3- to 17-fold, indicating a compensatory role, which could be explored for its therapeutic potential. Our study enhances our understanding of erythropoiesis and globin chain production through ontogeny.