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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: C. Haferlach, M. Vignetti, T. Haferlach, and B. Falini Response: NPM1-mutated AML is an entity irrespective of whether or not chromosomal aberrations are present Blood, November 12, 2009; 114(20): 4602 - 4603. [Full Text] [PDF] C. Haferlach, C. Mecucci, S. Schnittger, A. Kohlmann, M. Mancini, A. Cuneo, N. Testoni, G. Rege-Cambrin, A. Santucci, M. Vignetti, et al. AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features Blood, October 1, 2009; 114(14): 3024 - 3032. [Abstract] [Full Text] [PDF] S. Schnittger, W. Kern, C. Tschulik, T. Weiss, F. Dicker, B. 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Lowenberg MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia Blood, May 15, 2008; 111(10): 5078 - 5085. [Abstract] [Full Text] [PDF] T. Ottone, E. Ammatuna, S. Lavorgna, N. I. Noguera, F. Buccisano, A. Venditti, L. Gianni, M. Postorino, G. Federici, S. Amadori, et al. An Allele-Specific RT-PCR Assay to Detect Type A Mutation of the Nucleophosmin-1 Gene in Acute Myeloid Leukemia J. Mol. Diagn., May 1, 2008; 10(3): 212 - 216. [Abstract] [Full Text] [PDF] G. Wertheim and A. Bagg Nucleophosmin (NPM1) Mutations in Acute Myeloid Leukemia: An Ongoing (Cytoplasmic) Tale of Dueling Mutations and Duality of Molecular Genetic Testing Methodologies J. Mol. Diagn., May 1, 2008; 10(3): 198 - 202. [Abstract] [Full Text] [PDF] P. Szankasi, M. Jama, and D. W. Bahler A New DNA-Based Test for Detection of Nucleophosmin Exon 12 Mutations by Capillary Electrophoresis J. Mol. Diagn., May 1, 2008; 10(3): 236 - 241. [Abstract] [Full Text] [PDF] B. Falini, M. P. 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[Abstract] [Full Text] [PDF] R. E. Gale, C. Green, C. Allen, A. J. Mead, A. K. Burnett, R. K. Hills, D. C. Linch, and on behalf of the Medical Research Council Adult Le The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia Blood, March 1, 2008; 111(5): 2776 - 2784. [Abstract] [Full Text] [PDF] F. P. Kroschinsky, U. Schakel, R. Fischer, B. Mohr, U. Oelschlaegel, R. Repp, M. Schaich, S. Soucek, G. Baretton, G. Ehninger, et al. Cup-like acute myeloid leukemia: new disease or artificial phenomenon? Haematologica, February 1, 2008; 93(2): 283 - 286. [Abstract] [Full Text] [PDF] T. Haferlach Molecular Genetic Pathways as Therapeutic Targets in Acute Myeloid Leukemia Hematology, January 1, 2008; 2008(1): 400 - 411. [Abstract] [Full Text] [PDF] V. P. S. Rawat, S. Thoene, V. M. Naidu, N. Arseni, B. Heilmeier, K. Metzeler, K. Petropoulos, A. Deshpande, L. Quintanilla-Martinez, S. K. Bohlander, et al. Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depending on its N-terminal domain and is closely correlated with deregulated HOX gene expression in human acute myeloid leukemia Blood, January 1, 2008; 111(1): 309 - 319. [Abstract] [Full Text] [PDF] W. Zhang, J.-M. Navenot, N. M. Frilot, N. Fujii, and S. C. Peiper Association of Nucleophosmin Negatively Regulates CXCR4-Mediated G Protein Activation and Chemotaxis Mol. Pharmacol., November 1, 2007; 72(5): 1310 - 1321. [Abstract] [Full Text] [PDF] N. Bolli, I. Nicoletti, M. F. De Marco, B. Bigerna, A. Pucciarini, R. Mannucci, M. P. Martelli, A. Liso, C. Mecucci, F. Fabbiano, et al. Born to Be Exported: COOH-Terminal Nuclear Export Signals of Different Strength Ensure Cytoplasmic Accumulation of Nucleophosmin Leukemic Mutants Cancer Res., July 1, 2007; 67(13): 6230 - 6237. [Abstract] [Full Text] [PDF] B. Falini, I. Nicoletti, N. Bolli, M. P. Martelli, A. Liso, P. 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