Increase sensitivity to chemotherapeutical agents and cytoplasmatic interaction between NPM leukemic mutant and NF-κB in AML carrying NPM1 mutations

Cilloni, Daniela; Messa, Francesca; Rosso, Valentina; Arruga, Francesca; Defilippi, Ilaria; Carturan, Sonia; Catalano, Renata; Pautasso, Marisa; Panuzzo, Cristina; Nicoli, Paolo; Messa, Emanuela; Morotti, Alessandro; Iacobucci, Ilaria; Martinelli, Giovanni; Bracco, Enrico; Saglio, Giuseppe

doi:10.1038/leu.2008.68

Cited by 41 publications

(44 citation statements)

References 28 publications

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“…These results including ours show that NPM contributes to cancer pathogenesis as an oncogene. The NPM gene is mutated or rearranged in a number of hematological disorders (Cilloni et al, 2008), also suggesting that NPM functions as a proto-oncogene, but NPM gene mutation has not been detected in solid cancers (Jeong et al, 2007). In addition, NPM knockdown decreases cell viability, induces cellular senescence and growth arrest in CRC cells, also supporting its function as an oncogene (Wong et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of Nucleophosmin in Colorectal Carcinomas

Yang¹,

Zhang²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

Prognostic Role of Nucleophosmin in Colorectal Carcinomas

Yang¹,

Zhang²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…The authors hypothesized that this mechanism underlies the high sensitivity of AML with mutated NPM1 to chemotherapy. 91 …”

Section: Nf-kb Delocalizationmentioning

confidence: 99%

“…90 Cilloni et al 91 showed that mutated NPM1 bound to NF-kappaB and sequestered it in cytoplasm, leading to its inactivation. The authors hypothesized that this mechanism underlies the high sensitivity of AML with mutated NPM1 to chemotherapy.…”

Section: Nf-kb Delocalizationmentioning

confidence: 99%

Altered nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications

et al. 2009

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Nucleophosmin (NPM1) is a highly conserved nucleo-cytoplasmic shuttling protein that shows a restricted nucleolar localization. Mutations of NPM1 gene leading to aberrant cytoplasmic dislocation of nucleophosmin (NPMc þ ) occurs in about one third of acute myeloid leukaemia (AML) patients that exhibit distinctive biological and clinical features. We discuss the latest advances in the molecular basis of nucleophosmin traffic under physiological conditions, describe the molecular abnormalities underlying altered transport of nucleophosmin in NPM1-mutated AML and present evidences supporting the view that cytoplasmic nucleophosmin is a critical event for leukaemogenesis. We then outline how a highly specific immunohistochemical assay can be exploited to diagnose NPM1-mutated AML and myeloid sarcoma in paraffin-embedded samples by looking at aberrant nucleophosmin accumulation in cytoplasm of leukaemic cells. This procedure is also suitable for detection of haemopoietic multilineage involvement in bone marrow trephines. Moreover, use of immunohistochemistry as surrogate for molecular analysis can serve as first-line screening in AML and should facilitate implementation of the 2008 World Health Organization classification of myeloid neoplasms that now incorporates AML with mutated NPM1 (synonym: NPMc þ AML) as a new provisional entity. Finally, we discuss the future therapeutic perspectives aimed at reversing the altered nucleophosmin transport in AML with mutated NPM1.

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“…TNF-α is a proinflammatory cytokine that plays a role in the development of colorectal cancer, promoting tumor growth, survival and angiogenesis. In addition, this cytokine is responsible for signal transduction to pre-neoplastic epithelial cells in the colon (Cilloni et al, 2008). Popivanova et al (2008) showed that the inhibition of TNF-α reduces tumorigenesis in rats with cancer induced by AOM and dextran sulfate sodium (DSS).…”

Section: Discussionmentioning

confidence: 99%

“…Altered regulation of NF-kB is observed in many cancers. This transcription factor modulates the activation of genes related to cell proliferation, angiogenesis, metastasis, tumor promotion, inflammation, and apoptosis suppression (Watanabe et al, 2000;Lind et al, 2001;Cilloni et al, 2008;Meteoglu et al, 2008). Inhibition of the NF-kB signaling pathway is therefore a promising target for chemopreventive and chemotherapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Oral Concentrated Grape Juice Suppresses Expression of NF-kappa B, TNF-α and iNOS in Experimentally Induced Colorectal Carcinogenesis in Wistar Rats

Campanholo

Silva²,

Silva³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF-α. Methods: Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NFkB, TNF-and iNOS was evaluated by qPCR. Results: The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF-α and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration.

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Increase sensitivity to chemotherapeutical agents and cytoplasmatic interaction between NPM leukemic mutant and NF-κB in AML carrying NPM1 mutations

Cited by 41 publications

References 28 publications

Prognostic Role of Nucleophosmin in Colorectal Carcinomas

Prognostic Role of Nucleophosmin in Colorectal Carcinomas

Altered nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications

Oral Concentrated Grape Juice Suppresses Expression of NF-kappa B, TNF-α and iNOS in Experimentally Induced Colorectal Carcinogenesis in Wistar Rats

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