Lymphomas expressing ALK fusion protein(s) other than NPM-ALK

Brunangelo Falini, Karen Pulford, Alessandra Pucciarini, Antonino Carbone, Chris De Wolf-Peeters, Jacqueline Cordell, Marco Fizzotti, Antonella Santucci, Pier Giuseppe Pelicci, Stefano Pileri, Elias Campo, German Ott, Georges Delsol, David Y. Mason

Research output: Contribution to journalArticle

Abstract

The tumor cells in ALK-positive lymphoma ('ALKoma') usually express the product of the NPM-ALK chimeric gene, generated by the t(2;5) chromosomal translocation. However, 10% to 20% of ALK-positive lymphomas express ALK fusion protein(s) other than NPM-ALK, and in this report, we describe the immunohistologic and clinicopathologic features of 15 such cases. The absence of the NPM-ALK fusion gene was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 8 cases and by fluorescence in situ hybridization (FISH) analysis in a further 2 cases. In each case, ALK staining was restricted to the cytoplasm and the N-terminus of NPM to the nucleus (contrasting with lymphomas expressing NPM-ALK in which cytoplasmic as well as nuclear labeling is seen). However, in the course of screening 53 ALK- positive lymphomas, 2 biopsies were found that had a 'cytoplasm-only' ALK staining pattern but that nevertheless were shown to carry the (2;5) (by NPM staining and RT-PCR). The 15 cases resembled typical NPM-ALK-positive lymphomas in that all were of T or null phenotype, usually occurred in young male patients, and frequently presented with advanced disease associated with systemic symptoms and extranodal involvement. Moreover their prognosis was excellent and indistinguishable from that of classical t(2;5)positive tumors, but was clearly different from that of ALK-negative anaplastic large-cell lymphomas. These results suggest that lymphomas carrying variants of the NPM- ALK fusion protein can be detected by immunostaining for ALK and NPM and also that they can be grouped with classical t(2;5)-positive tumors as a single entity (ALK-positive lymphoma or 'ALKoma') that shows a better prognosis than ALK-negative anaplastic large-cell lymphoma.

Original languageEnglish
Pages (from-to)3509-3515
Number of pages7
JournalBlood
Volume94
Issue number10
Publication statusPublished - Nov 15 1999

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Tumors
Lymphoma
Fusion reactions
Polymerase chain reaction
RNA-Directed DNA Polymerase
Genes
Proteins
Biopsy
Anaplastic Large-Cell Lymphoma
Labeling
Staining and Labeling
Reverse Transcriptase Polymerase Chain Reaction
Screening
Fluorescence
Cells
Cytoplasm
Neoplasms
Genetic Translocation
Gene Fusion
Fluorescence In Situ Hybridization

ASJC Scopus subject areas

  • Hematology

Cite this

Falini, B., Pulford, K., Pucciarini, A., Carbone, A., De Wolf-Peeters, C., Cordell, J., ... Mason, D. Y. (1999). Lymphomas expressing ALK fusion protein(s) other than NPM-ALK. Blood, 94(10), 3509-3515.

Lymphomas expressing ALK fusion protein(s) other than NPM-ALK. / Falini, Brunangelo; Pulford, Karen; Pucciarini, Alessandra; Carbone, Antonino; De Wolf-Peeters, Chris; Cordell, Jacqueline; Fizzotti, Marco; Santucci, Antonella; Pelicci, Pier Giuseppe; Pileri, Stefano; Campo, Elias; Ott, German; Delsol, Georges; Mason, David Y.

In: Blood, Vol. 94, No. 10, 15.11.1999, p. 3509-3515.

Research output: Contribution to journalArticle

Falini, B, Pulford, K, Pucciarini, A, Carbone, A, De Wolf-Peeters, C, Cordell, J, Fizzotti, M, Santucci, A, Pelicci, PG, Pileri, S, Campo, E, Ott, G, Delsol, G & Mason, DY 1999, 'Lymphomas expressing ALK fusion protein(s) other than NPM-ALK', Blood, vol. 94, no. 10, pp. 3509-3515.
Falini B, Pulford K, Pucciarini A, Carbone A, De Wolf-Peeters C, Cordell J et al. Lymphomas expressing ALK fusion protein(s) other than NPM-ALK. Blood. 1999 Nov 15;94(10):3509-3515.
Falini, Brunangelo ; Pulford, Karen ; Pucciarini, Alessandra ; Carbone, Antonino ; De Wolf-Peeters, Chris ; Cordell, Jacqueline ; Fizzotti, Marco ; Santucci, Antonella ; Pelicci, Pier Giuseppe ; Pileri, Stefano ; Campo, Elias ; Ott, German ; Delsol, Georges ; Mason, David Y. / Lymphomas expressing ALK fusion protein(s) other than NPM-ALK. In: Blood. 1999 ; Vol. 94, No. 10. pp. 3509-3515.
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abstract = "The tumor cells in ALK-positive lymphoma ('ALKoma') usually express the product of the NPM-ALK chimeric gene, generated by the t(2;5) chromosomal translocation. However, 10{\%} to 20{\%} of ALK-positive lymphomas express ALK fusion protein(s) other than NPM-ALK, and in this report, we describe the immunohistologic and clinicopathologic features of 15 such cases. The absence of the NPM-ALK fusion gene was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 8 cases and by fluorescence in situ hybridization (FISH) analysis in a further 2 cases. In each case, ALK staining was restricted to the cytoplasm and the N-terminus of NPM to the nucleus (contrasting with lymphomas expressing NPM-ALK in which cytoplasmic as well as nuclear labeling is seen). However, in the course of screening 53 ALK- positive lymphomas, 2 biopsies were found that had a 'cytoplasm-only' ALK staining pattern but that nevertheless were shown to carry the (2;5) (by NPM staining and RT-PCR). The 15 cases resembled typical NPM-ALK-positive lymphomas in that all were of T or null phenotype, usually occurred in young male patients, and frequently presented with advanced disease associated with systemic symptoms and extranodal involvement. Moreover their prognosis was excellent and indistinguishable from that of classical t(2;5)positive tumors, but was clearly different from that of ALK-negative anaplastic large-cell lymphomas. These results suggest that lymphomas carrying variants of the NPM- ALK fusion protein can be detected by immunostaining for ALK and NPM and also that they can be grouped with classical t(2;5)-positive tumors as a single entity (ALK-positive lymphoma or 'ALKoma') that shows a better prognosis than ALK-negative anaplastic large-cell lymphoma.",
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AU - Falini, Brunangelo

AU - Pulford, Karen

AU - Pucciarini, Alessandra

AU - Carbone, Antonino

AU - De Wolf-Peeters, Chris

AU - Cordell, Jacqueline

AU - Fizzotti, Marco

AU - Santucci, Antonella

AU - Pelicci, Pier Giuseppe

AU - Pileri, Stefano

AU - Campo, Elias

AU - Ott, German

AU - Delsol, Georges

AU - Mason, David Y.

PY - 1999/11/15

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N2 - The tumor cells in ALK-positive lymphoma ('ALKoma') usually express the product of the NPM-ALK chimeric gene, generated by the t(2;5) chromosomal translocation. However, 10% to 20% of ALK-positive lymphomas express ALK fusion protein(s) other than NPM-ALK, and in this report, we describe the immunohistologic and clinicopathologic features of 15 such cases. The absence of the NPM-ALK fusion gene was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 8 cases and by fluorescence in situ hybridization (FISH) analysis in a further 2 cases. In each case, ALK staining was restricted to the cytoplasm and the N-terminus of NPM to the nucleus (contrasting with lymphomas expressing NPM-ALK in which cytoplasmic as well as nuclear labeling is seen). However, in the course of screening 53 ALK- positive lymphomas, 2 biopsies were found that had a 'cytoplasm-only' ALK staining pattern but that nevertheless were shown to carry the (2;5) (by NPM staining and RT-PCR). The 15 cases resembled typical NPM-ALK-positive lymphomas in that all were of T or null phenotype, usually occurred in young male patients, and frequently presented with advanced disease associated with systemic symptoms and extranodal involvement. Moreover their prognosis was excellent and indistinguishable from that of classical t(2;5)positive tumors, but was clearly different from that of ALK-negative anaplastic large-cell lymphomas. These results suggest that lymphomas carrying variants of the NPM- ALK fusion protein can be detected by immunostaining for ALK and NPM and also that they can be grouped with classical t(2;5)-positive tumors as a single entity (ALK-positive lymphoma or 'ALKoma') that shows a better prognosis than ALK-negative anaplastic large-cell lymphoma.

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