TCRγδ+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRγδ+ T-cells

• Published in: Leukemia Vol. 20; no. 3; pp. 505 - 513
• Main Authors: SANDBERG, Y, ALMEIDA, J, SAN MIGUEL, J. F, ORFAO, A, LANGERAK, A. W, GONZALEZ, M, LIMA, M, BARCENA, P, SZCZEPANSKI, T, VAN GASTEL-MOL, E. J, WIND, H, BALANZATEGUI, A, VAN DONGEN, J. J. M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-03-2006; Nature Publishing Group
• Subjects: Anemia; Antigens; Biological and medical sciences; CD11b antigen; CD11c antigen; CD16 antigen; CD5 antigen; CD56 antigen; CD57 antigen; CD7 antigen; CD8 antigen; Gene rearrangement; Hematologic and hematopoietic diseases; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes; Lymphocytes T; Medical sciences; Neutropenia; Pancytopenia; Pathogenesis; Patients; Splenomegaly; T cell receptors; Thrombocytopenia; Thymus; Human; TCRG; Immunophenotype; γ/δ T cell receptor; Selection; TCRD; Malignant hemopathy; antigen-selection; Antigen; LGL; Chronic; T-LGL leukemia; Lymphoproliferative syndrome; T-Lymphocyte; Large Granular Lymphocyte Leukemia; Vγ/Vδ usage
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2404112

T-cell large granular lymphocytes (LGL) proliferations range from reactive expansions of activated T cells to T-cell leukemias and show variable clinical presentation and disease course. The vast majority of T-LGL proliferations express TCRαβ. Much less is known about the characteristics and pathogenesis of TCRγδ+ cases. We evaluated 44 patients with clonal TCRγδ+ T-LGL proliferations with respect to clinical data, immunophenotype and TCR gene rearrangement pattern. TCRγδ+ T-LGL leukemia patients had similar clinical presentations as TCRαβ+ T-LGL leukemia patients. Their course was indolent and 61% of patients were symptomatic. The most common clinical manifestations were chronic cytopenias – neutropenia (48%), anemia (23%), thrombocytopenia (9%), pancytopenia (2%) – and to a lesser extent splenomegaly (18%). Also multiple associated autoimmune (34%) and hematological (14%) disorders were found. Leukemic LGLs were predominantly positive for CD2, CD5, CD7, CD8, and CD57, whereas variable expression was seen for CD16, CD56, CD11b, and CD11c. The Vγ9/Vδ2 immunophenotype was found in 48% of cases and 43% of cases was positive for Vδ1, reflecting the TCR-spectrum of normal TCRγδ+ T-cells in adult PB. Identification of the well-defined post-thymic Vδ2-Jδ1 selection determinant in all evaluable Vγ9+/Vδ2+ patients, is suggestive of common (super)antigen involvement in the pathogenesis of these TCRγδ+ T-LGL leukemia patients.