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 & 1 others Brunangelo Falini

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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
JournalBlood
Volume108
Issue number13
DOIs
Publication statusPublished - Dec 15 2006

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Acute Myeloid Leukemia
Cell Lineage
Karyotype
Erythroid Cells
Biopsy
Myeloid Cells
Fibroblasts
Paraffin
Endothelium
Anti-Idiotypic Antibodies
Exons
Bone
Lasers
Genes
Bone Marrow
nucleophosmin
Mutation
Antibodies
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Pasqualucci, L., Liso, A., Martelli, M. P., Bolli, N., Pacini, R., Tabarrini, A., ... Falini, B. (2006). Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: Impact on WHO classification. Blood, 108(13), 4146-4155. https://doi.org/10.1182/blood-2006-06-026716

Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia : Impact on WHO classification. / Pasqualucci, Laura; Liso, Arcangelo; Martelli, Maria Paola; Bolli, Niccolò; Pacini, Roberta; Tabarrini, Alessia; Carini, Manola; Bigerna, Barbara; Pucciarini, Alessandra; Mannucci, Roberta; Nicoletti, Ildo; Tiacci, Enrico; Meloni, Giovanna; Specchia, Giorgina; Cantore, Nicola; Di Raimondo, Francesco; Pileri, Stefano; Mecucci, Cristina; Mandelli, Franco; Martelli, Massimo Fabrizio; Falini, Brunangelo.

In: Blood, Vol. 108, No. 13, 15.12.2006, p. 4146-4155.

Research output: Contribution to journalArticle

Pasqualucci, L, Liso, A, Martelli, MP, Bolli, N, Pacini, R, Tabarrini, A, Carini, M, Bigerna, B, Pucciarini, A, Mannucci, R, Nicoletti, I, Tiacci, E, Meloni, G, Specchia, G, Cantore, N, Di Raimondo, F, Pileri, S, Mecucci, C, Mandelli, F, Martelli, MF & Falini, B 2006, 'Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: Impact on WHO classification', Blood, vol. 108, no. 13, pp. 4146-4155. https://doi.org/10.1182/blood-2006-06-026716
Pasqualucci, Laura ; Liso, Arcangelo ; Martelli, Maria Paola ; Bolli, Niccolò ; Pacini, Roberta ; Tabarrini, Alessia ; Carini, Manola ; Bigerna, Barbara ; Pucciarini, Alessandra ; Mannucci, Roberta ; Nicoletti, Ildo ; Tiacci, Enrico ; Meloni, Giovanna ; Specchia, Giorgina ; Cantore, Nicola ; Di Raimondo, Francesco ; Pileri, Stefano ; Mecucci, Cristina ; Mandelli, Franco ; Martelli, Massimo Fabrizio ; Falini, Brunangelo. / Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia : Impact on WHO classification. In: Blood. 2006 ; Vol. 108, No. 13. pp. 4146-4155.
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AU - Pasqualucci, Laura

AU - Liso, Arcangelo

AU - Martelli, Maria Paola

AU - Bolli, Niccolò

AU - Pacini, Roberta

AU - Tabarrini, Alessia

AU - Carini, Manola

AU - Bigerna, Barbara

AU - Pucciarini, Alessandra

AU - Mannucci, Roberta

AU - Nicoletti, Ildo

AU - Tiacci, Enrico

AU - Meloni, Giovanna

AU - Specchia, Giorgina

AU - Cantore, Nicola

AU - Di Raimondo, Francesco

AU - Pileri, Stefano

AU - Mecucci, Cristina

AU - Mandelli, Franco

AU - Martelli, Massimo Fabrizio

AU - Falini, Brunangelo

PY - 2006/12/15

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N2 - 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.

AB - 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.

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