Mutational landscape and its clinical significance in paroxysmal nocturnal hemoglobinuria

作者：Fangfei Chen, Shimin Hu, Jing Ruan, Miao Chen, Bing Han · 发表于：Blood Cancer Journal · 年份：2021 · DOI：10.1038/s41408-021-00451-1 · 被引用次数：8 · 研究领域：Complement system in diseases、Coagulation, Bradykinin, Polyphosphates, and Angioedema、Renal Diseases and Glomerulopathies

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder caused by mutation of the X-linked PIGA gene, resulting in a deficient expression of glycosylphosphatidylinositol-anchored proteins, such as CD55 and CD59 1 . Patients with PNH may present with hemolytic anemia, thrombosis, and bone marrow failure. The loss of CD55 and CD59 renders PNH erythrocytes susceptible to intravascular hemolysis and thrombosis. There is a close relationship between PNH and aplastic anemia (AA). The clinical picture may shift from one to the other during the course of disease 2 . Genes commonly mutated in myeloid neoplasms have been tested in patients with AA, and some carry prognostic significance 3 . For instance, mutations in PIGA , BCOR , and BCORL1 correlate with a better response to immunosuppressive therapy and a longer duration of overall survival and progression-free survival in patients with AA, whereas mutations in DNMT3A, RUNX1 , JAK2 , JAK3 , and CSMD1 are associated with a worse prognosis. However, studies on the mutations of myeloid cancer-related genes in PNH and on the mechanism of PNH clonal expansion are limited or inconclusive 4 , 5 . On the other hand, thrombosis is the most common complication in patients with PNH 6 , 7 . Although the risk of thrombosis correlates with the PNH clone size, thrombotic events do occur in patients with small PNH clones. Recent studies have uncovered that mutations rather than PIGA may function as additiona...