Fulminant clonal expansion of large granular lymphocytes: Characterization of their morphology, phenotype, genotype, and function

Abstract

A 39-year-old woman exhibited abrupt malignant transformation of the large granular lymphocytes (LGL) after a chronic course of T,-lymphoproliferative disease (T,-LPD). The T,-lymphocytes were CD2+, CD3-, CD8-, CD16+, Leu7-, and Leul9+ with morphologic characteristics of LGL. Newly appearing LGL were much larger and had more prominent azurophilic granules. Although fundamentally they had the same phenotype as the LGL in chronic stage, they showed increased Ia-like antigen and decreased CD16 antigen expressions. Immunoglobulin (Ig) G-kappa type monoclonal component was detected in the patient's serum. The LGL showed a germ-line configuration for T-cell receptor (TCR) beta and gamma chain genes, whereas the clonal chromosomal abnormalities indicated the neoplastic nature of the LGL. The LGL exhibited competent natural killer (NK), interleukin 2 (IL2) activated killer (AK), and antibody-dependent cell-mediated cytotoxicity (ADCC) activities. The LGL may have derived from NK cells at their mature stage with prethymic phenotype and may have influenced the homeostasis of the patient's humoral immune response.

Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells

“…Two patients who attained CR further received allogeneic BM transplantation (no. 19) and autologous PB cell transplantation (no. 22).…”

ERK couples chronic survival of NK cells to constitutively activated Ras in lymphoproliferative disease of granular lymphocytes (LDGL)

“…Features of aggressive NK-LDGL include large numbers of circulating NK cells, hepatosplenomegaly, and a median survival time of only a few months. Most cases of aggressive NK-LDGL occur in the Far East and are the result of EBV infection (Ohno et al, 1988;Taniwaki et al, 1990). Patients with chronic NK-LDGL have lymphocytosis that is often associated with bone marrow failure consisting of moderate anemia and/or neutropenia (Tefferi et al, 1994).…”

Epstein-Barr Virus-Induced Infectious Mononucleosis after Two Separate Episodes of Virus-Associated Hemophagocytic Syndrome

“…He had been well and active in public service except for occasional mild flu-like symptoms during the six-year period after the second episode of HPS, which was reported in our previous publication (7). In both episodes of HPS, steroid pulse therapy was effective and led to complete recovery (7) 51 Cr-releasing assay showed about 60% killing of K562 cells at an effector/target ratio of 20, as described previously (7,8).…”