Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one-third of adults with AML. AML NPM1mutis recognized as a separate entity in the World Health Organization classification of AML. Clinical and survival data suggest that patients with this form of AML often have a more favorable prognosis, which may be due to the immunogenicity created by the mutations in the NPM1 protein. Consequently, AML with NPM1mutcan be considered an immunogenic subtype of AML. However, the underlying mechanisms of this immunogenicity and associated favorable survival outcomes need to be further investigated. Immune checkpoint molecules, such as the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, play important roles in leukemogenesis through their maintenance of an immunosuppressive tumor microenvironment. Preclinical trials have shown that the use of PD-1/PD-L1 checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with AML NPM1mutmay be better suited to immunogenic strategies that are based on the inhibition of the PD-1 immune checkpoint pathway than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PD-1 inhibitors.
急性髓系白血病（AML）是一种血液与骨髓的恶性疾病，其特征是异常髓系祖细胞不受控制的克隆性增殖。核仁磷酸蛋白1（NPM1）基因突变是AML中最常见的遗传异常，约三分之一的成人AML患者原始细胞中可检测到该突变。世界卫生组织AML分类体系已将NPM1突变型AML列为独立疾病亚型。临床与生存数据表明，此类AML患者通常预后更佳，这可能源于NPM1蛋白突变产生的免疫原性。因此，NPM1突变型AML可被视为具有免疫原性的AML亚型。然而，这种免疫原性及其相关良好生存结局的内在机制仍需深入研究。程序性细胞死亡蛋白-1（PD-1）及其配体PD-L1等免疫检查点分子，通过维持免疫抑制性肿瘤微环境在白血病发生发展中发挥重要作用。临床前试验表明，PD-1/PD-L1检查点抑制剂在实体瘤和淋巴瘤治疗中，与新型联合疗法配合时疗效最佳。相较于无此突变的患者，NPM1突变型AML患者可能更适合基于PD-1免疫检查点通路抑制的免疫治疗策略，这表明患者的基因谱特征也可为PD-1抑制剂的最佳临床应用提供指导。
Immunotherapeutic Potential of Mutated NPM1 for the Treatment of Acute Myeloid Leukemia
肿瘤(癌症)患者之家