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Acute Myeloid Leukemia with Mutated Nucleophosmin (NPM1): Molecular, Pathological, and Clinical Features

  • Brunangelo Falini
Chapter
Part of the Cancer Treatment and Research book series (CTAR, volume 145)

Abstract

The NPM1 gene encodes for nucleophosmin, a nucleolus-located shuttling protein that is involved in multiple cell functions, including regulation of ribosome biogenesis, control of centrosome duplication and preservation of ARF tumor suppressor integrity. The NPM1 gene is specifically mutated in about 30% acute myeloid leukemia (AML) but not in other human neoplasms. Mutations cause crucial changes at the C-terminus of the NPM1 protein that are responsible for the aberrant nuclear export and accumulation of NPM1 mutants in the cytoplasm of leukemic cells. Diagnosis of AML with mutated NPM1 can be done using molecular techniques, immunohistochemistry (looking at cytoplasmic dislocation of nucleophosmin that is predictive of NPM1 mutations) and Western blotting with antibodies specifically directed against NPM1 mutants. Because of its distinctive molecular, pathological, immunophenotypic and prognostic features, AML with mutated NPM1 (synonym: NPMc+ AML) has been included, as a new provisional entity, in the 2008 World Health Organization (WHO) classification of myeloid neoplasms.

Keywords

Acute Myeloid Leukemia Acute Myeloid Leukemia Patient Anaplastic Large Cell Lymphoma Ribosome Biogenesis Nuclear Export Signal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC). We would like to thank Mrs. Claudia Tibido` for her excellent secretarial assistance and Dr. Geraldine Anne Boyd for her help in editing this paper. B. Falini applied for a patent on clinical use of NPM1 mutants.

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.From the Institute of HematologyUniversity of PerugiaPerugiaItaly

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