Anaplastic Large-Cell Lymphomas of T-Cell and Null-Cell Phenotype Express Cytotoxic Molecules

• Published in: Blood Vol. 88; no. 10; pp. 4005 - 4011
• Main Authors: Foss, Hans-Dieter, Anagnostopoulos, loannis, Araujo, Iguaracyra, Assaf, Chalid, Demel, Gudrun, Kummer, J.Alain, Hummel, Michael, Stein, Harald
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.11.1996; The Americain Society of Hematology
• Subjects: Biological and medical sciences; Biomarkers; Cell Differentiation; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Granzymes; Hematologic and hematopoietic diseases; Hodgkin Disease - metabolism; Hodgkin Disease - pathology; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphocyte Activation; Lymphocytes, Null - metabolism; Lymphocytes, Null - pathology; Lymphoma, B-Cell - metabolism; Lymphoma, B-Cell - pathology; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, T-Cell - metabolism; Lymphoma, T-Cell - pathology; Lymphoma, T-Cell, Peripheral - metabolism; Lymphoma, T-Cell, Peripheral - pathology; Medical sciences; Membrane Glycoproteins - biosynthesis; Neoplasm Proteins - biosynthesis; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Perforin; Pore Forming Cytotoxic Proteins; Reed-Sternberg Cells - metabolism; Reed-Sternberg Cells - pathology; Serine Endopeptidases - biosynthesis; T-Lymphocytes, Cytotoxic - metabolism; T-Lymphocytes, Cytotoxic - pathology; Immunohistochemistry; Molecular hybridization; In situ; Beta-Peptide chain; Cytotoxicity; Proteins; Granzyme B; Lymphoproliferative syndrome; T-Lymphocyte; Genetics; Null cell; Human; T cell receptor; Serine endopeptidases; Enzyme; Exploration; Malignant hemopathy; Large cell lymphoma; Non Hodgkin lymphoma; Polymerase chain reaction; Pathology; Peptidases; Gene rearrangement; Hydrolases; Molecular biology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V88.10.4005.bloodjournal88104005

To further specify the cellular origin and nature of anaplastic large-cell lymphoma (ALCL) and its relationship to other lymphoid neoplasms, particularly Hodgkin's disease (HD), we investigated the presence of cytotoxic molecules in a large well-characterized series of these tumors. For expression of the cytotoxic molecules perforin and granzyme B, in situ hybridization (ISH) and immunohistology were used, respectively. Overall, 23 of 25 ALCLs of T/null phenotype and five (three mixed cellularity and two nodular sclerosis) of 57 HD cases showed the presence of perforin transcripts and/or granzyme B molecules in neoplastic cells. Polymerase chain reaction (PCR) analysis of ALCLs showed that most (10 of 11) cases of null-cell ALCL (null-ALCL) contained a clonal rearrangement of T-cell receptor β-chain genes, as did T-cell ALCL (T-ALCL; 9 of 10 cases). However, both cytotoxic molecules and clonally rearranged T-cell receptor β-chain genes were absent in seven of seven and eight of nine cases of B-cell ALCL (B-ALCL), respectively. These data show that all or nearly all T-ALCLs, irrespective of the clinical subform or the lack of T-cell-associated molecules, are derived from activated cytotoxic T cells. The same appears to be true for the neoplastic cells of rare HD cases. These findings indicate that T-ALCLs are different from B-ALCLs and the majority of HD cases, and suggest that some HD cases, especially those with T-cell antigen-positive tumor cells, may be closely related to T-ALCL, at least in terms of cellular origin.