Altogether, these pieces of evidence point to NPM1-mutated AML as a founder genetic event that defines a distinct leukemia entity accounting for approximately one-third of all AML.
Areas covered: Available techniques include multi-color flow cytometry (MFC) of leukemia associated immunophenotypes (LAIP), quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) for detecting fusion and mutated genes (RUNX1-RUNX1T1, CBFB-MYH11, and NPM1), overexpression of genes such as WT1, and next generation sequencing (NGS) for MRD.
By analyzing the enrichment of differentially‑expressed genes in chemical and genetic perturbation datasets, it was found that genes, which were upregulated in the FLT3 high expression group had myeloid lymphoid leukemia‑ and nucleophosmin 1‑like signatures, indicating that the overexpression of FLT3 may use the same mechanism to promote leukemia.
Future studies should focus on clarifying how NPM mutants promote leukemia, integrating NPMc+ AML in the upcoming World Health Organization leukemia classification, and eventually developing specific antileukemic drugs.
However, miR-10a/b overexpression was not associated with complete remission rate, and did not have an impact on both leukemia free survival and overall survival time in non-M3 AML patients without NPM1 mutation.
In this review, we focus on the leukemia-associated NPM1 C-terminal domain and describe its structure, function, and the effect exerted by leukemic mutations.
Interestingly, a cytogenetic analysis disclosed a leukemia clone with the karyotype of 46, XY, t(5;17)(q35;q12), which generated nucleophosmin (NPM)-retinoic acid receptor alpha fusion (RARA) fusion transcripts.
OCI/AML3 cells also displayed typical phenotypic features of NPMc+ AML, that is, expression of macrophage markers and lack of CD34, and the immunocytochemical hallmark of this leukemia subtype, that is, the aberrant cytoplasmic expression of NPM.
Our findings suggest that while K-RAS mutations are infrequent in CN-AML, activating K-RAS mutations may cooperate with mutated NPM1 to induce leukemia.
Our results indicate that INPP4B promotes leukemia cell survival via SGK3 activation, and INPP4B might be a potential target in the treatment of NPM1-mutated AML.
Possible implications for choice of MRD method, timing of MRD monitoring, and guidance of therapy are discussed in general and in some detail for certain types of leukemia with specific molecular markers to monitor, including core binding factor (CBF)-leukemias and NPM1-mutated leukemias.
Potent graft-versus-leukemia effect after reduced-intensity allogeneic SCT for intermediate-risk AML with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD.
Significant associations were found between the risk of relapse or the risk of death during complete remission and the leukemia genotype of mutant NPM1 without FLT3-ITD (hazard ratio, 0.44; 95% confidence interval [CI], 0.32 to 0.61), the mutant CEBPA genotype (hazard ratio, 0.48; 95% CI, 0.30 to 0.75), and the MLL-PTD genotype (hazard ratio, 1.56; 95% CI, 1.00 to 2.43), as well as receipt of a transplant from an HLA-matched related donor (hazard ratio, 0.60; 95% CI, 0.44 to 0.82).