Centennial development of paroxysmal nocturnal hemoglobinuria research in Peking Union Medical College Hospital

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematopoietic stem cell (HSC) disease. A somatic phosphatidylinositol glycan-A (PIGA) gene mutation in HSCs translates into abnormal biosynthesis of glycosyl phosphatidylinositol (GPI) anchors on the cell surface. The absence of GPI-anchored complements regulators leads to complement-driven blood cell lysis. Hemolysis and chronic anemia are the most common clinical manifestations, while bone marrow failure is a rare but life-threatening complication. Thrombosis is the leading cause of mortality. Transfusion and supportive care have been introduced as symptomatic treatments since the early decades of the last century. Eculizumab, a monoclonal antibody that blocks terminal complement at C5, is a breakthrough medicine that changed the standard treatment methods of PNH. However, in cases where eculizumab is not accessible, allogeneic HSC transplantation could be an alternative strategy for refractory and aplastic patients. The Peking Union Medical College Hospital (PUMCH) is approaching its centennial anniversary in 2021. The first case of PNH in China was reported by physicians at PUMCH in the 1950s. During the past century, generations of hematologists established the largest cohort of PNH patients in China while continuously developing novel laboratory tests for this disease. They collaborated with investigators of basic science on the pathogenetic mechanisms of bone marrow failure and thrombosis. Although great historical changes have impacted academic progress, the spirit of perseverance, commitment, and innovation in older generations is passed on to the next generations. In this paper, we summarize the clinical evolution of PNH treatment along with basic science at PUMCH, which in turn facilitates great progress in PNH in the era of the 21st century in China.