Nucleophosmin1 (NPM1) abnormality in hematologic malignancies, and therapeutic targeting of mutant NPM1 in acute myeloid leukemia

The frequency of NPM1 mutations in childhood acute myeloid leukemia

BACKGROUND Mutations in the nucleophosmin (NPM1) gene have been solely associated with childhood acute myeloid leukemia (AML). We evaluated the frequency of NPM1 mutations in childhood AML, their relation to clinical and cytogenetic features and the presence of common FLT3 and RAS mutations. RESULTS NPM1 mutations were found in 8% of cases. They involved the typical type 'A' mutation and one ...

Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia.

Mutations in the nucleophosmin 1 (NPM1) gene are considered a founder event in the pathogenesis of acute myeloid leukemia (AML). To address the role of clonal evolution in relapsed NPM1-mutated (NPM1mut) AML, we applied high-resolution, genome-wide, single-nucleotide polymorphism array profiling to detect copy number alterations (CNAs) and uniparental disomies (UPDs) and performed comprehensive...

How does the NPM1 mutant induce leukemia?

NPM1 is the most frequently mutated gene in AML and the role of the NPM1 mutant in acute myeloid leukemia along with its leukemogenic potential are still under investigation.NPM1 genetic alterations can contribute to leukemogenesis through the direct oncogenic effect of the mutant protein and the concomitant loss of one functional allele. Npm1 loss determines tumor development in the mouse whil...

A novel mechanism of NPM1 cytoplasmic localization in acute myeloid leukemia: the recurrent gene fusion NPM1-HAUS1.

NPM1 mutation is associated with leukemia cutis in acute myeloid leukemia with monocytic features.