Institute of Hematology and Center for Hemato-Oncological Research (CREO), University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy.
Department of Medical and Molecular Genetics, King's College, London, United Kingdom.
Blood Cancer Discov. 2024 Jan 8;5(1):8-20. doi: 10.1158/2643-3230.BCD-23-0144.
NPM1-mutated acute myeloid leukemia (AML) represents the largest molecular subgroup of adult AML. NPM1-mutated AML is recognizable by molecular techniques and immunohistochemistry, which, when combined, can solve difficult diagnostic problems (including identification of myeloid sarcoma and NPM1 mutations outside exon 12). According to updated 2022 European LeukemiaNet (ELN) guidelines, determining the mutational status of NPM1 (and FLT3) is a mandatory step for the genetic-based risk stratification of AML. Monitoring of measurable residual disease (MRD) by qRT-PCR, combined with ELN risk stratification, can guide therapeutic decisions at the post-remission stage. Here, we review the criteria for appropriate diagnosis and molecular monitoring of NPM1-mutated AML.
NPM1-mutated AML represents a distinct entity in the 2022 International Consensus Classification and 5th edition of World Health Organization classifications of myeloid neoplasms. The correct diagnosis of NPM1-mutated AML and its distinction from other AML entities is extremely important because it has clinical implications for the management of AML patients, such as genetic-based risk stratification according to 2022 ELN. Monitoring of MRD by qRT-PCR, combined with ELN risk stratification, can guide therapeutic decisions at the post-remission stage, e.g., whether or not to perform allogeneic hematopoietic stem cell transplantation.
NPM1 突变型急性髓系白血病（AML）代表成人 AML 中最大的分子亚群。NPM1 突变型 AML 可通过分子技术和免疫组织化学识别，当两者结合使用时，可以解决困难的诊断问题（包括髓肉瘤和 NPM1 突变体的鉴定）。根据 2022 年更新的欧洲白血病网络（ELN）指南，确定 NPM1（和 FLT3）的突变状态是 AML 基于遗传风险分层的强制性步骤。通过 qRT-PCR 监测可测量的残留疾病（MRD），结合 ELN 风险分层，可以指导缓解后阶段的治疗决策。在这里，我们回顾了 NPM1 突变型 AML 的适当诊断和分子监测标准。
NPM1 突变型 AML 在 2022 年国际共识分类和第五版世界卫生组织髓系肿瘤分类中代表一个独特的实体。正确诊断 NPM1 突变型 AML 并将其与其他 AML 实体区分开来非常重要，因为它对 AML 患者的管理具有临床意义，例如根据 2022 年 ELN 进行基于遗传的风险分层。通过 qRT-PCR 监测 MRD，结合 ELN 风险分层，可以指导缓解后阶段的治疗决策，例如是否进行异基因造血干细胞移植。
