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.
ARTICLES|
February 1, 1996
Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease
HT Yee,
HT Yee
Department of Pathology, New York University Medical Center, New York, USA.
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M Ponzoni,
M Ponzoni
Department of Pathology, New York University Medical Center, New York, USA.
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A Merson,
A Merson
Department of Pathology, New York University Medical Center, New York, USA.
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M Goldstein,
M Goldstein
Department of Pathology, New York University Medical Center, New York, USA.
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A Scarpa,
A Scarpa
Department of Pathology, New York University Medical Center, New York, USA.
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M Chilosi,
M Chilosi
Department of Pathology, New York University Medical Center, New York, USA.
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F Menestrina,
F Menestrina
Department of Pathology, New York University Medical Center, New York, USA.
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S Pittaluga,
S Pittaluga
Department of Pathology, New York University Medical Center, New York, USA.
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C de Wolf-Peeters,
C de Wolf-Peeters
Department of Pathology, New York University Medical Center, New York, USA.
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M Shiota,
M Shiota
Department of Pathology, New York University Medical Center, New York, USA.
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S Mori,
S Mori
Department of Pathology, New York University Medical Center, New York, USA.
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G Frizzera,
G Frizzera
Department of Pathology, New York University Medical Center, New York, USA.
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G Inghirami
G Inghirami
Department of Pathology, New York University Medical Center, New York, USA.
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Blood (1996) 87 (3): 1081–1088.
Citation
HT Yee, M Ponzoni, A Merson, M Goldstein, A Scarpa, M Chilosi, F Menestrina, S Pittaluga, C de Wolf-Peeters, M Shiota, S Mori, G Frizzera, G Inghirami; Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease. Blood 1996; 87 (3): 1081–1088. doi: https://doi.org/10.1182/blood.V87.3.1081.bloodjournal8731081
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