Mutations of the nucleophosmin (NPM1) gene have recently been described in patients with acute myeloid leukemia (AML). To clarify the prevalence as well as the clinical impact of this mutation, we investigated 1485 patients with AML for NPM1 exon 12 mutations using fragment analysis. A 4 bp insert was detected in 408 of 1485 patients (27.5%). Sequence analysis revealed known mutations (type A, ...

The NPM1 mutation is the most frequent genetic alteration thus far identified in acute myeloid leukemia (AML). Despite progress in the clinical and biological characterization of NPM1-mutated AML, the role of NPM1 mutation in leukemogenesis in vivo has not been fully elucidated. We report a novel mouse model that conditionally expresses the most common human NPM1 mutation (type A) in the hemato...

OBJECTIVE Mutations of the nucleophosmin (NPM1) gene are considered as the most frequent acute myeloid leukemia (AML)-associated genetic lesion, reported with various incidences in different studies, and type A (NPM1-A) is the most frequent type. However, since most series in the literature report on the features of all patients regardless of the type of mutation, NPM1-A(+) cases have not been ...

Abstract Mutations of the nucleophosmin (NPM1) gene, encoding for a nucleolar multifunctional protein, occur in approximately one-third adult acute myeloid leukemia (AML). NPM1-mutated AML exhibits unique molecular, pathological, and clinical features, which led to its recognition as distinct entity 2017 World Health Organization (WHO) classification neoplasms. Although WHO criteria diagnosis a...

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 ...

The nucleolus has been recently described as a stress sensor. The nucleoplasmic translocation of nucleolar protein nucleophosmin (NPM1) is a hallmark of nucleolar stress; however, the causes of this translocation and its connection to p53 activation are unclear. Using single live-cell imaging and the redox biosensors, we demonstrate that nucleolar oxidation is a general response to various cell...

The ubiquitin-like SUMO system functions by a cyclic process of modification and demodification, and recent data suggest that the nucleolus is a site of sumoylation-desumoylation cycles. For example, the tumour suppressor ARF stimulates sumoylation of nucleolar proteins. Here, we show that the nucleolar SUMO-specific protease SENP3 is associated with nucleophosmin (NPM1), a crucial factor in ri...

NPM1/nucleophosmin is frequently overexpressed in various tumors, although the oncogenic role of NPM1 remains unclear. Here we revealed the link between NPM1 and nuclear factor-κB (NF-κB), a master regulator of inflammation. We found that NPM1 knockdown decreased NF-κB-mediated transcription of selected target genes by decreasing the recruitment of NF-κB p65 to the gene promoters. NPM1 is direc...

Downlo tein accumulation at DNA double-strand breaks (DSB) is essential for genome stability; however, the nisms governing these events are not fully understood. Here, we report a new role for the nucleophosrotein NPM1 in these mechanisms. Thr199-phosphorylated NPM1 (pT199-NPM1) is recruited to nuclear amage foci induced by ionizing radiation (IR). Foci formation is impaired by depletion of the...

ownloade tein accumulation at DNA double-strand breaks (DSB) is essential for genome stability; however, the nisms governing these events are not fully understood. Here, we report a new role for the nucleophosrotein NPM1 in these mechanisms. Thr199-phosphorylated NPM1 (pT199-NPM1) is recruited to nuclear amage foci induced by ionizing radiation (IR). Foci formation is impaired by depletion of t...