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Blood, 1 February 2007, Vol. 109, No. 3, pp. 874-885. Prepublished online as a Blood First Edition Paper on October 2, 2006September 28, 2006; DOI 10.1182/blood-2006-07-012252. This Article Full Text (PDF) All Versions of this Article: blood-2006-07-012252v1 blood-2006-07-012252v2 109/3/874    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Falini, B. Articles by Mecucci, C. Search for Related Content PubMed PubMed Citation Articles by Falini, B. Articles by Mecucci, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 10, 2006 Accepted September 11, 2006 Invited review: Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NMPc+ AML): biological and clinical features Brunangelo Falini*, Ildo Nicoletti, Massimo Fabrizio Martelli, and Cristina Mecucci Institute of Hematology, University of Perugia, Perugia, Italy Institute of Internal Medicine, University of Perugia, Perugia, Italy * Corresponding author; email: faliniem{at}unipg.it. The Nucleophosmin (NPM1) gene encodes for a multifunctional nucleo-cytoplasmic shuttling protein which is mainly localized in the nucleolus. NPM1 mutations occur in 50-60% of adult acute myeloid leukemia with normal karyotype (AML-NK) and generate NPM mutants that localize aberrantly in the leukemic cells cytoplasm; hence the term NPM-cytoplasmic positive (NPMc+ AML). Cytoplasmic NPM accumulation is caused by the concerted action of two alterations at mutant C-terminus, i.e. changes of tryptophan(s) 288 and 290 (or only 290) and creation of an additional nuclear export signal (NES) motif. NPMc+ AML shows increased frequency in adults and female sex, wide morphologic spectrum, multilineage involvement, high frequency of FLT3-ITD, CD34-negativity, and distinct gene expression profile. Analysis of mutated NPM has important clinical and pathological applications. Immunohistochemical detection of cytoplasmic NPM predicts NPM1 mutations and helps rationalize cytogenetic/molecular studies in AML. NPM1 mutations in absence of FLT3-ITD identify a prognostically favourable subgroup in the heterogeneous AML-NK category. Due to their frequency and stability, NPM1 mutations may become a new tool for monitoring minimal residual disease in AML-NK. Future studies should focus on clarifying how NPM mutants promote leukemia, integrating NPMc+ AML in the upcoming World Health Organization leukemia classification, and eventually developing specific anti-leukemic drugs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. S. Laughlin, M. W. Becker, J. L. Liesveld, D. A. Mulford, C. N. Abboud, P. Brown, and P. G. Rothberg Rapid Method for Detection of Mutations in the Nucleophosmin Gene in Acute Myeloid Leukemia J. Mol. Diagn., July 1, 2008; 10(4): 338 - 345. [Abstract] [Full Text] [PDF] F. Lo-Coco, A. Cuneo, F. Pane, D. Cilloni, D. Diverio, M. Mancini, N. Testoni, A. Bardi, B. Izzo, N. Bolli, et al. Prognostic impact of genetic characterization in the GIMEMA LAM99P multicenter study for newly diagnosed acute myeloid leukemia Haematologica, July 1, 2008; 93(7): 1017 - 1024. [Abstract] [Full Text] [PDF] M. Jongen-Lavrencic, S. M. Sun, M. K. Dijkstra, P. 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