Large Granular Lymphocyte Proliferation with the Natural Killer-Cell Phenotype

Abstract

Lymphoproliferated disorders involving large granular lymphocytes (LGL) can be divided into a common T-cell subset (CD3+, CD8+) and a rarer natural killer (NK)-cell subset (CD2+, CD3-). The immunophenotype, clinical pathologic features, and cytogenetic and molecular genetic analyses are reported for seven patients with NK-cell-LGL proliferation. The typical immunophenotype was CD2+, CD3-, CD4-, CD11b+, and CD16+ or CD56+. A low but variable percentage of cells were CD8+ or CD57+. Unusual phenotypes with CD2- (1 of 7), CD11b- (1 of 7), or CD16-/CD56- (1 of 7) cells were seen. Strong NK-cell activity was observed in all cases, indicating that none of the NK-cell markers (CD11b, CD16, CD56, CD57) is essential for NK-cell activity. One patient died shortly after diagnosis from coexistent refractory multiple myeloma and another patient died within 1 month from the LGL proliferation. The other patients had been followed for 12 to 70 months, with a median follow-up period of 38 months. There was no progression of their LGL proliferation. Lymphocyte counts varied from 3.3 x 10(3)/microL to 58.4 x 10(3)/microL at the time of diagnosis. Unexplained anemia and neutropenia were observed in one patient. Cytogenetic abnormalities were detected in two of four patients studied with t(6;12) in one and der(5), der(6), and der(11) in the other. The approximately T gamma and T beta genes were in the germline configuration and Epstein-Barr virus DNA was undetectable in five of five patients studied. Natural killer-cell LGL proliferations were morphologically indistinguishable from T-cell LGL proliferations. However, the two were immunophenotypically and genotypically distinct and NK-cell activity was consistently observed in the former. Most of the NK-cell proliferations also were chronic indolent disorders and the incidence of associated cytopenias seemed to be lower than T-cell LGL proliferations.

A long‐term study of patients with chronic natural killer cell lymphocytosis

“…In comparison with a group of 68 patients with T-LGL leukaemia evaluated at our institution, the incidences of severe anaemia and neutropenia were signi®cantly lower in patients with CNKL (6% and 19%, respectively) than those with T-LGL leukaemia (19% and 40%) (Dhodapkar et al, 1994a). The incidence of associated cytopenias in CNKL was similarly low in other series (Chan et al, 1992). In T-LGL leukaemia constitutive expression of the Fas ligand in the clonally expanded cell population may facilitate target cell apoptosis and contribute to the pathogenesis of the observed cytopenias (Perzova & Loughran, 1997).…”

Clinical, Hematologic, and Immunophenotypic Characterization of Canine Large Granular Lymphocytosis

“…Some patients with CD3 Ϫ NK cell LGL lymphocytosis have a chronic clinical course with no evidence of clonality, suggestive of a reactive process. 5,12 Human patients with clonal proliferation of CD3p…”

Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I.

“…tus). The antibody-dependent cellular cytotoxicity assay was performed as described (24). For Western blot analysis,107 cells from the F8 cellline, the MT2 HTLV-I-positive cellline, and the CEM HTLV-I-negative cell line were lysed in solubilizing buffer [10% (vol/vol) Triton X-100/5% (vol/vol) deoxycholate/1% SDS] and immunoprecipitated with a 1:5000 dilution of rabbit anti-peptide antisera (anti-Tax-C, from W. C. Greene, University of California, San Francisco) and protein G-Sepharose.…”