NPM1-Mutated AML: Deciphering the Molecular and Clinical Puzzle in the Era of Novel Treatment Strategies.

The aberrant localization of the mutated nucleophosmin (NPM1) protein in the cytoplasm is the hallmark of the development of acute myeloid leukemia (AML); the gene, located in the nucleolus, codes for a protein that normally shuttles between the nucleus and the cytoplasm of the normal hematopoietic cells. Patients harboring NPM1 mutations are diagnosed as having NPM1-mutated AMLs, which are types of leukemia with distinct clinical and laboratory characteristics. The essential diagnostics for investigating NPM1-mutated AMLs, the interactions with concomitant mutations affecting prognosis and the therapeutic interventions that the treatment of such patients requires are discussed in this review. Novel investigational agents in current clinical trials are also highlighted, along with the roles of exportin 1 (XPO1), menin-KMT2A inhibitors and immunotherapy in NPM1-mutated AMLs. This review focuses on critically evaluating the available data and aims to reveal the secrets of NPM1-mutated AMLs.