Creation of a nuclear export signal (NES) motif and loss of tryptophans (W) 288 and 290 (or 290 only) at the COOH terminus of nucleophosmin (NPM) are both crucial for NPM aberrant cytoplasmic accumulation in acute myelogenous leukemia (AML) carrying NPM1 mutations. Hereby, we clarify how these COOH-terminal alterations functionally cooperate to delocalize NPM to the cytoplasm. Using a Rev(1.4)-...

NPM-ALK⁺ T-cell anaplastic large-cell lymphoma (ALCL) is an aggressive type of cancer. Standard treatment of NPM-ALK⁺ ALCL is CHOP polychemotherapy. Although patients initially respond favorably to CHOP, resistance, relapse, and death frequently occur. Recently, selective targeting of ALK has emerged as an alternative therapeutic strategy. ASP3026 is a second-generation ALK inhibitor that can o...

NPM is a major nucleolar multifunctional protein involved in ribosome biogenesis, centrosome duplication, cell-cycle progression, apoptosis, cell differentiation, and sensing cellular stress. Alarmins are endogenous molecules released from activated cells and/or dying cells, which activate the immune system and cause severe damage to cells and tissue organs. In the present work, stimulation of ...

Aim. Continuous positive airway pressure (CPAP) masks are a key factor in patient compliance. This program assessed the performance of a new nasal pillows mask (NPM) on a variety of new and established obstructive sleep apnea (OSA) patients using CPAP therapy. Methods. Five programs were developed to assess the new NPM [AirFit P10, ResMed] on naïve patients; patients established on another NPM;...

Because activation of p53 can trigger cell cycle arrest and apoptosis, it is necessary for a cell to suppress this activation until it is absolutely required for survival. The mechanisms underlying this important regulatory event are poorly understood. Here we show that nucleophosmin (NPM) acts as a natural repressor of p53 by setting a threshold for p53 activation in response to UV radiation. ...

We showed previously that nucleophosmin (NPM), a nucleolar phosphoprotein, is recognized by sera from (NZW x BXSB)F1 (WB) mice, a model of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome. In the present study we analysed the prevalence and kinetics of anti-NPM autoantibodies in WB mice by a solid-phase ELISA with recombinant human (rh) NPM as the antigen and showed that most m...

One third of acute myeloid leukemias (AMLs) are characterized by the aberrant cytoplasmic localization of nucleophosmin (NPM) due to mutations within its putative nucleolar localization signal. NPM mutations are mutually exclusive with major AML-associated chromosome rearrangements and are frequently associated with a normal karyotype, suggesting that they are critical during leukemogenesis. Th...

UV damage activates cellular stress signaling pathways, causes DNA helix distortions and inhibits transcription by RNA polymerases I and II. In particular, the nucleolus, which is the site of RNA polymerase I transcription and ribosome biogenesis, disintegrates following UV damage. The disintegration is characterized by reorganization of the subnucleolar structures and change of localization of...

Nucleophosmin-anaplastic lymphoma kinase-expressing (NPM-ALK+ ) T-cell lymphoma is an aggressive neoplasm that is more commonly seen in children and young adults. The pathogenesis of NPM-ALK+ T-cell lymphoma is not completely understood. Wild-type ALK is a receptor tyrosine kinase that is physiologically expressed in neural tissues during early stages of human development, which suggests that A...

Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is a chimeric protein expressed in a subset of cases of anaplastic large cell lymphoma (ALCL) for which constitutive expression represents a key oncogenic event. The ALK signaling pathway is complex and probably involves functional redundancy between various signaling substrates of ALK. Despite numerous studies on signaling mediators, the molec...