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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4146-4155. Prepublished online as a Blood First Edition Paper on August 22, 2006; DOI 10.1182/blood-2006-06-026716. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-06-026716v1 108/13/4146    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Pasqualucci, L. Articles by Falini, B. Search for Related Content PubMed PubMed Citation Articles by Pasqualucci, L. Articles by Falini, B. Related Collections Neoplasia Oncogenes and Tumor Suppressors Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: impact on WHO classification Laura Pasqualucci, Arcangelo Liso, Maria Paola Martelli, Niccolò Bolli, Roberta Pacini, Alessia Tabarrini, Manola Carini, Barbara Bigerna, Alessandra Pucciarini, Roberta Mannucci, Ildo Nicoletti, Enrico Tiacci, Giovanna Meloni, Giorgina Specchia, Nicola Cantore, Francesco Di Raimondo, Stefano Pileri, Cristina Mecucci, Franco Mandelli, Massimo Fabrizio Martelli, and Brunangelo Falini From the Institute of Hematology, University of Perugia, Italy; the Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY; the Institute of Hematology, University of Foggia, Italy; the Institute of Hematology, University of Bari, Italy; the Institute of Internal Medicine, University of Perugia, Italy; the Institute of Hematology, University "La Sapienza," Rome, Italy; the Hematology Service, "Moscati" Hospital, Avellino, Italy; the Institute of Hematology, "Ferrarotto" Hospital, Catania, Italy; and the Institute of Hematology, Policlinico S. Orsola, Bologna, Italy. Because of a lack of specific clonality markers, information on lineage involvement and cell of origin of acute myeloid leukemia with normal karyotype (AML-NK), is missing. Because Nucleophosmin (NPM) gene is frequently mutated in AML-NK and causes aberrant NPM cytoplasmic localization (NPMc+), it was used as an AML lineage clonality marker. Clonal NPM exon 12 mutations were detected in myeloid, monocytic, erythroid, and megakaryocytic cells but not in fibroblasts or endothelia that were laser-microdissected from 3 patients with NPMc+ AML. Aberrant cytoplasmic expression of mutated NPM proteins was identified with anti-NPM antibodies in 2 or more myeloid hemopoietic cell lineages in 99 (61.5%) of 161 of NPMc+ AML paraffin-embedded bone marrow biopsies; lymphoid involvement was excluded in 3 investigated cases. These findings suggest that NPMc+ AML derives from either a common myeloid or earlier progenitor. Immunohistochemical studies show that varying combinations and ratios of NPMc+ leukemic cells from distinct lineages are responsible for heterogeneity within each French-American-British (FAB) classification type and for NPMc+ AML falling into different FAB categories. These findings question the value of FAB criteria in subdividing the WHO category of "AML not otherwise characterized" and suggest that, for clinical use, NPMc+ AML be provisionally regarded as a separate AML with prognostic significance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: NPM1 mutation in AML: WHO and why? David Grimwade Blood 2006 108: 3965. [Full Text] [PDF] This article has been cited by other articles: 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. Gorello, F. Mandelli, C. Mecucci, and M. F. Martelli Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias Haematologica, April 1, 2007; 92(4): 519 - 532. [Abstract] [Full Text] [PDF] B. Falini, I. Nicoletti, M. F. Martelli, and C. Mecucci Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features Blood, February 1, 2007; 109(3): 874 - 885. [Abstract] [Full Text] [PDF]

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