Yamazaki Hirohito
Division of Transfusion Medicine, Kanazawa University Hospital.
Rinsho Ketsueki. 2018;59(6):711-715. doi: 10.11406/rinketsu.59.711.
Acquired aplastic anemia (AA) is an autoimmune disease caused by T cells specific to hematopoietic stem cells (HSCs). The presence of HLA allele-lacking leukocytes due to uniparental disomy of the short arm of chromosome 6 (6pUPD) or allelic mutations strongly indicates the involvement of such cytotoxic T cells in the pathogenesis of AA. Attempts to improve treatment outcomes by intensification of immunosuppressive therapy (IST) have been unsuccessful. Eltrombopag (EPAG), a thrombopoietin receptor agonist, has recently emerged as a novel therapeutic agent for AA. EPAG directly acts on HSCs and stimulates proliferation, thereby achieving remission in approximately 40% AA patients refractory to IST. However, some cases develop chromosomal aberrations during treatment. Because somatic mutations are common in patients with AA, verifying whether EPAG induces clonal proliferation or evolution of mutant HSCs is critical.
获得性再生障碍性贫血（AA）是一种由针对造血干细胞（HSC）的特异性T细胞引起的自身免疫性疾病。由于6号染色体短臂单亲二体性（6pUPD）或等位基因突变导致缺乏HLA等位基因的白细胞的存在，强烈表明此类细胞毒性T细胞参与了AA的发病机制。通过强化免疫抑制治疗（IST）来改善治疗效果的尝试均未成功。艾曲泊帕（EPAG），一种血小板生成素受体激动剂，最近已成为AA的一种新型治疗药物。EPAG直接作用于造血干细胞并刺激其增殖，从而使大约40%对IST难治的AA患者实现缓解。然而，一些病例在治疗期间会出现染色体畸变。由于体细胞突变在AA患者中很常见，因此验证EPAG是否诱导突变造血干细胞的克隆增殖或进化至关重要。
