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 MartelliBrunangelo Falini

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)4146-4155
Number of pages10
Issue number13
Publication statusPublished - Dec 15 2006

ASJC Scopus subject areas

  • Hematology


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