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

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 HBM levels in relation to other hemoglobin chains in neonatal, pediatric, and adult blood. Furthermore, 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. This study enhances our understanding of erythropoiesis and globin chain production through ontogeny.