New research led by AABB Foundation Hall of Fame members Angelo D’Alessandro, PhD; and James C. Zimring, MD, PhD, explored the genetic underpinnings of red blood cell (RBC) metabolic heterogeneity and storage outcomes.
Published in
Blood, the study identified a novel mechanism of ferroptosis, or iron-dependent lipid peroxidation, as the main driver of the storage lesion of stored packed red blood cells. The authors identified more than 400 gene-metabolite associations using RBCs from 350 genetically diverse outbred mice. Among the findings, the ferrireductase Steap3 emerged as a key regulator of lipid peroxidation through a ferroptosis-related process, which favors the untimely removal of storage-damaged from the bloodstream of the recipient, which could result in poor post-transfusion recovery.
During human validation, the team discovered an association between STEAP3 polymorphism and RBC iron content, lipid peroxidation and hemolysis in more than 13,000 blood donors. These polymorphisms and their related genes were prevalent in donors of African descent and were linked to lower hemoglobin increments in transfusion recipients in a vein-to-vein database.
The Impact of the AABB Foundation
The AABB Foundation is current
accepting applications for the Early-Career Scientific Research Grants Program’s 2025 cycle through Dec. 1. Foundation grant recipients receive an award of up to $100,000 to further investigator-initiated, original research in blood banking, transfusion medicine or biotherapies.
