Nucleophosmin 1(NPM1)mutation is a core molecular marker in adult acute myeloid leukemia(AML)and an ideal target for as-sessing subclinical disease burden(i.e.,minimal residual disease[MRD]).This mutation has a significant clinical value in disease classification,treatment selection,and prognosis evaluation.In this review,we integrate the latest research advances and discuss the clinical applicability of targeted therapies,chemotherapy combined with anti-CD33 monoclonal antibodies,and allogeneic hematopoietic stem cell transplanta-tion(allo-hematopoietic stem-cell transplantation).This review highlights the importance of dynamic MRD monitoring to optimize long-term disease management.We particularly focus on the mechanisms of drug resistance in NPM1-mutated AML(e.g.,B-cell lymphoma 2[BCL-2]/myeloid cell leukemia 1[MCL-1]imbalance and metabolic adaptations)and characteristics of the Chinese population(mutation fre-quency,co-mutation profiles,and treatment response).This review aims to provide clinicians with a stratified diagnosis and treatment framework for NPM1-mutated AML as well as theoretical foundations for future research directions.

Nucleophosmin 1(NPM1)mutation is a core molecular marker in adult acute myeloid leukemia(AML)and an ideal target for as-sessing subclinical disease burden(i.e.,minimal residual disease[MRD]).This mutation has a significant clinical value in disease classification,treatment selection,and prognosis evaluation.In this review,we integrate the latest research advances and discuss the clinical applicability of targeted therapies,chemotherapy combined with anti-CD33 monoclonal antibodies,and allogeneic hematopoietic stem cell transplanta-tion(allo-hematopoietic stem-cell transplantation).This review highlights the importance of dynamic MRD monitoring to optimize long-term disease management.We particularly focus on the mechanisms of drug resistance in NPM1-mutated AML(e.g.,B-cell lymphoma 2[BCL-2]/myeloid cell leukemia 1[MCL-1]imbalance and metabolic adaptations)and characteristics of the Chinese population(mutation fre-quency,co-mutation profiles,and treatment response).This review aims to provide clinicians with a stratified diagnosis and treatment framework for NPM1-mutated AML as well as theoretical foundations for future research directions.