Institute of Haematology, Centro Ricerche Emato-Oncologiche (CREO), Ospedale S. Maria della Misericordia, University of Perugia, Perugia, Italy.
Leukemia. 2021 Nov;35(11):3113-3126. doi: 10.1038/s41375-021-01222-4. Epub 2021 Apr 20.
Mutations of Nucleophosmin (NPM1) are the most common genetic abnormalities in adult acute myeloid leukaemia (AML), accounting for about 30% of cases. NPM1-mutated AML has been recognized as distinct entity in the 2017 World Health Organization (WHO) classification of lympho-haematopoietic neoplasms. WHO criteria allow recognition of this leukaemia entity and its distinction from AML with myelodysplasia-related changes, AML with BCR-ABL1 rearrangement and AML with RUNX1 mutations. Nevertheless, controversial issues include the percentage of blasts required for the diagnosis of NPM1-mutated AML and whether cases of NPM1-mutated myelodysplasia and chronic myelomonocytic leukaemia do exist. Evaluation of NPM1 and FLT3 status represents a major pillar of the European LeukemiaNet (ELN) genetic-based risk stratification model. Moreover, NPM1 mutations are particularly suitable for assessing measurable residual disease (MRD) since they are frequent, stable at relapse and do not drive clonal haematopoiesis. Ideally, combining monitoring of MRD with the ELN prognostication model can help to guide therapeutic decisions. Here, we provide examples of instructive cases of NPM1-mutated AML, in order to provide criteria for the appropriate diagnosis and therapy of this frequent leukaemia entity.
核磷蛋白（NPM1）突变是成人急性髓系白血病（AML）中最常见的遗传异常，约占病例的 30%。在 2017 年世界卫生组织（WHO）淋巴造血肿瘤分类中，NPM1 突变型 AML 已被认为是一种独特的实体。WHO 标准允许识别这种白血病实体，并将其与伴骨髓发育异常相关改变的 AML、伴 BCR-ABL1 重排的 AML 和伴 RUNX1 突变的 AML 区分开来。然而，仍存在一些争议性问题，包括诊断 NPM1 突变型 AML 所需的原始细胞百分比，以及是否存在 NPM1 突变型骨髓增生异常和慢性粒单核细胞白血病的病例。评估 NPM1 和 FLT3 状态是欧洲白血病网络（ELN）基于遗传的风险分层模型的主要支柱之一。此外，NPM1 突变特别适合评估可测量残留疾病（MRD），因为它们频繁出现、在复发时稳定且不会驱动克隆性造血。理想情况下，将 MRD 监测与 ELN 预后模型相结合，可以帮助指导治疗决策。在这里，我们提供了一些 NPM1 突变型 AML 的实例，以便为这种常见白血病实体的适当诊断和治疗提供标准。
