Molecular characterization of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease

Herman Terence Yee, Maurilio Ponzoni, Alex Merson, Marsha Goldstein, Aldo Scarpa, Marco Chilosi, Fabio Menestrina, Stefania Pittaluga, Christine De Wolf-Peeters, Mami Shiota, Shigeo Mori, Glauco Frizzera, Giorgio Inghirami

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Abstract

The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase- polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT- PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.

Original languageEnglish
Pages (from-to)1081-1088
Number of pages8
JournalBlood
Volume87
Issue number3
Publication statusPublished - Feb 1 1996

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Anaplastic Large-Cell Lymphoma
Hodgkin Disease
Genes
Polymerase chain reaction
RNA-Directed DNA Polymerase
Cells
Southern Blotting
Reverse Transcriptase Polymerase Chain Reaction
Immunohistochemistry
Reed-Sternberg Cells
Null Lymphocytes
Gene Rearrangement
Cytogenetic Analysis
Sclerosis
nucleophosmin
Immune Sera
T-Lymphocytes
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hematology

Cite this

Yee, H. T., Ponzoni, M., Merson, A., Goldstein, M., Scarpa, A., Chilosi, M., ... Inghirami, G. (1996). Molecular characterization of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease. Blood, 87(3), 1081-1088.

Molecular characterization of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease. / Yee, Herman Terence; Ponzoni, Maurilio; Merson, Alex; Goldstein, Marsha; Scarpa, Aldo; Chilosi, Marco; Menestrina, Fabio; Pittaluga, Stefania; De Wolf-Peeters, Christine; Shiota, Mami; Mori, Shigeo; Frizzera, Glauco; Inghirami, Giorgio.

In: Blood, Vol. 87, No. 3, 01.02.1996, p. 1081-1088.

Research output: Contribution to journalArticle

Yee, HT, Ponzoni, M, Merson, A, Goldstein, M, Scarpa, A, Chilosi, M, Menestrina, F, Pittaluga, S, De Wolf-Peeters, C, Shiota, M, Mori, S, Frizzera, G & Inghirami, G 1996, 'Molecular characterization of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease', Blood, vol. 87, no. 3, pp. 1081-1088.
Yee, Herman Terence ; Ponzoni, Maurilio ; Merson, Alex ; Goldstein, Marsha ; Scarpa, Aldo ; Chilosi, Marco ; Menestrina, Fabio ; Pittaluga, Stefania ; De Wolf-Peeters, Christine ; Shiota, Mami ; Mori, Shigeo ; Frizzera, Glauco ; Inghirami, Giorgio. / Molecular characterization of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease. In: Blood. 1996 ; Vol. 87, No. 3. pp. 1081-1088.
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abstract = "The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase- polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT- PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.",
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AU - Goldstein, Marsha

AU - Scarpa, Aldo

AU - Chilosi, Marco

AU - Menestrina, Fabio

AU - Pittaluga, Stefania

AU - De Wolf-Peeters, Christine

AU - Shiota, Mami

AU - Mori, Shigeo

AU - Frizzera, Glauco

AU - Inghirami, Giorgio

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N2 - The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase- polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT- PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.

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