Greiner Jochen, Mohamed Eithar, Fletcher Daniel M, Schuler Patrick J, Schrezenmeier Hubert, Götz Marlies, Guinn Barbara-Ann
Department of Internal Medicine III, University Hospital Ulm, 89081 Ulm, Germany.
Department of Internal Medicine, Diakonie Hospital Stuttgart, 70176 Stuttgart, Germany.
Cancers (Basel). 2024 Oct 10;16(20):3443. doi: 10.3390/cancers16203443.
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 NPM1 is 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 NPM1 can 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 NPM1 may 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）是一种血液和骨髓的恶性疾病，其特征是异常髓系祖细胞的不受控制的克隆增殖。核仁磷酸蛋白1（NPM1）基因突变是AML中最常见的基因异常，在约三分之一的成年AML患者的原始细胞中可检测到。AML NPM1在世界卫生组织的AML分类中被视为一个独立的实体。临床和生存数据表明，这种形式的AML患者通常预后较好，这可能是由于NPM1蛋白突变产生的免疫原性。因此，伴有NPM1的AML可被视为AML的一种免疫原性亚型。然而，这种免疫原性的潜在机制以及相关的良好生存结果需要进一步研究。免疫检查点分子，如程序性细胞死亡蛋白1（PD-1）及其配体PD-L1，通过维持免疫抑制性肿瘤微环境在白血病发生中起重要作用。临床前试验表明，在实体瘤和淋巴瘤中使用PD-1/PD-L1检查点抑制剂在新的治疗组合中效果最佳。与没有这种突变的患者相比，伴有AML NPM1的患者可能更适合基于抑制PD-1免疫检查点途径的免疫原性策略，这表明患者的基因背景也可能为使用PD-1抑制剂的最佳实践提供依据。
