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

Leukemia
D CilloniGiuseppe Saglio

Abstract

Mutations in nucleophosmin (NPM) exon 12 and the resulting delocalization of NPM into the cytoplasm are the most specific and frequent cellular events in acute myeloid leukemia patients (AML) with normal karyotype. Cytoplasmatic NPM (NPMc+) is associated with responsiveness to chemotherapy and better prognosis. The activation of nuclear factor-kappaB (NF-kappaB) has been demonstrated to occur in a subset of AML patients and is thought to induce resistance to many chemotherapeutical agents. In this study, we demonstrate the increased in vitro sensitivity of NPMc+ cells to chemotherapeutical agents and their reduced NF-kappaB activity. Furthermore, we provide evidence of the interaction between NPMc+ and NF-kappaB in the cytoplasm, resulting in the sequestration and inactivation of NF-kappaB. The cytosolic localization and consequent inactivation of NF-kappaB justifies the reduced NF-kappaB DNA-binding activity observed in NPMc+ patients. These data, taken together, may provide a possible explanation for the increased rate of chemosensitivity observed among the NPMc+ patients.

References

Jan 10, 2002·Critical Care Medicine·Uwe Senftleben, Michael Karin
May 2, 2002·Cell·Sankar Ghosh, Michael Karin
May 11, 2002·Nature Reviews. Cancer·Michael KarinZhi-Wei Li
Feb 21, 2003·The Journal of Biological Chemistry·Tetsuro TakebayashiMasanori Hatakeyama
Jan 7, 2004·Nature Reviews. Drug Discovery·Michael KarinQ May Wang
Apr 17, 2004·The Journal of Biological Chemistry·Sanjit K DharDaret K St Clair
Sep 24, 2004·Cancer Cell·Bharat B Aggarwal
Jan 22, 2005·The New England Journal of Medicine·Brunangelo FaliniUNKNOWN GIMEMA Acute Leukemia Working Party
Oct 4, 2005·Molecular and Cellular Biology·Emanuela ColomboPier Giuseppe Pelicci
Mar 17, 2006·Cancer Research·Emanuela ColomboPier Giuseppe Pelicci
Aug 2, 2007·Haematologica·Daniela CilloniGiuseppe Saglio

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Citations

Sep 23, 2009·Current Opinion in Oncology·Brunangelo FaliniMaria Paola Martelli
Jul 13, 2012·BMC Complementary and Alternative Medicine·Chuan Bian LimYan Zhao
Nov 7, 2009·Pharmacogenomics·Christophe Roumier, Meyling H Cheok
Jul 17, 2013·Immunopharmacology and Immunotoxicology·Karina Lucrecia CalvoFabiana García
Jul 16, 2014·Expert Review of Hematology·Muneera Al-Hussaini, John F DiPersio
Sep 19, 2009·Expert Review of Anticancer Therapy·Natalia Meani, Myriam Alcalay
Mar 27, 2010·Human Pathology·Cláudia Malheiros Coutinho-CamilloFernando Augusto Soares
Jul 1, 2009·European Journal of Haematology·Mike ZangenbergPeter Hokland
Mar 23, 2011·Traffic·Carolin BierRoland H Stauber
Apr 11, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Yu-Feng YangYan-Fang Xie
Mar 5, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Vanessa Maria de Lima Pazine CampanholoNora Manoukian Forones
Feb 23, 2010·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Felicetto FerraraSalvatore Palmieri
Oct 7, 2015·Cancer Immunology, Immunotherapy : CII·Susanne HofmannBarbara-Ann Guinn
May 8, 2021·Journal of Cellular Physiology·Fateme Karimi DermaniRazieh Amini
Jun 3, 2021·Cancers·Mateus de Oliveira LisboaSabine Mai

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