NPM 1 Mutations in AML-The Landscape in 2023

Author Department

Hematology/Oncology

Document Type

Article, Peer-reviewed

Publication Date

2-2023

Abstract

Acute myeloid leukemia (AML) represents 80% of acute leukemia in adults and is characterized by clonal expansion of hematopoietic stem cells secondary to genomic mutations, rendering a selective growth advantage to the mutant clones. NPM1mut is found in around 30% of AML and clinically presents with leukocytosis, high blast percentage and extramedullary involvement. Considered as a "gate-keeper" mutation, NPM1mut appears to be a "first hit" in the process of leukemogenesis and development of overt leukemia. Commonly associated with other mutations (e.g., FLT 3, DNMT3A, TET2, SF3B1), NPM1 mutation in AML has an important role in diagnosis, prognosis, treatment and post-treatment monitoring. Several novel therapies targeting NPM1 are being developed in various clinical phases with demonstration of efficacy. In this review, we summarize the pathophysiology of the NPM1 gene mutation in AML, clinical implications and the novel targeted therapies to date.

Keywords: CAR-T cells; XPO1 inhibitors; acute myeloid leukemia (AML); arsenic trioxide; exportin 1; menin inhibitors; minimal residual disease (MRD); nucleophosmin (NPM1) mutation.

PMID

36831522

Share

COinS