Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.

Phorbol esters inhibit the binding of insulin to its receptors on U-937 monocyte-like and HL-60 promyelocytic leukemia human cell lines. Within 20-30 min, exposure of these cells to 12-0-tetradecanoylphorbol 13-acetate (TPA) at 37 "C results in a 50 % reduction of the specific binding of '251-insulin. Half-maximal inhibition occurs at 1 nM TPA. Other tumor-promoting phorbol esters also inhibit '251-insulin binding in a dose-dependent manner which parallels their known promoting activity in vivo. TPA does not alter the degradation of the hormone nor does it induce any shedding of its receptors in the medium. The effect of phorbol esters is dependent on temperature and cell type. It is less prominent at 22 "C than at 37 "C. It is reversible within 2 h at 37 "C. TPA reduces the binding of insulin predominantly by increasing its dissociation rate. This effect results in an accelerated turnover of the hormone on its receptors.Phorbol esters are tetracyclic diterpenes that are potent tumor-promoting agents in some tissues (e.g. mouse skin) [1,2] while they induce differentiation in others [3-51. They bind to specific receptors on the cell surface [6] and evoke multiple biological and biochemical changes when added to cultured cells ([7] for review). The nature of the responses initiated by these compounds in vivo as well as in vitro has many similarities with those of growth-stimulating polypeptide hormones such as epidermal growth factor (EGF). Recently is has been demonstrated that phorbol esters reduce the number [8] or the affinity [9,10] of EGF receptors, while they clearly potentiate the biological effects of EGF [lo-131.In addition, these tumor promoters possess insulin-like activity (stimulation of glucose transport and oxidation) in a number of cell types [I41 and they facilitate the growthpromoting action of insulin on 3T3 fibroblastic cells [ l l -131. The binding of insulin to its receptors has been reported to be unaltered by phorbol esters in 3T3 [9] and Hela cells [15]. Since this has also been the case for the binding of nerve growth factor, concanavalin A, multiplication-stimulating activity and low-density lipoproteins to their receptors [9], it was thought that tumor promoters specifically alter the EGF binding. This observation might be related, however, to the cell types under investigation. Thus, in his study of EGF and phorbol receptors in mouse OTT-6050 embryonal carcinoma cells [16], Salomon incidentally reported that TPA (12-0-tetradecanoylphorbol 13-acetate) inhibits the binding of '" I-insulin.In the present investigation we have examined the effect of phorbol esters on the insulin-receptor interaction in the U-937 monocyte-like [5] and the HL-60 promyelocytic leukemia [3,4] human cell lines. The HL-60 cells possess specific receptors for insulin [17-191 and phorbol esters [20] and they are sensitive to the action of these agents [14,21].Ahhreviutions. Hepes, 4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid; TPA, 12-0-tetradecanoylphorbol 13-acetate; EGF, epidermal growth factor.Ou...

The authors describe a patient who presented an association of hairy cell leukemia (HCL) and large granular lymphocyte (LGL) leukemia. An eventual relationship between these two rare entities is analyzed. Hairy cells (HCs) were present in the blood, bone marrow, and spleen. An excess of LGLs was found only in the blood and bone marrow. After splenectomy the patient received an alpha 2-interferon (alpha 2-IFN) treatment. The HCs surface phenotype was mu+delta+kappa+, CD20+, and CD25+. The LGLs consisted in CD3+, CD8+, HNK1+, WT31+ T lymphocytes. These were absent in the spleen. alpha 2-IFN treatment resulted in the disappearance of the HCs in the blood and bone marrow, whereas the LGLs remained unchanged. Before alpha 2-IFN treatment, peripheral blood cells, predominantly LGLs, exerted low cytotoxicity that increased up to a normal level after treatment. Using Southern blotting the authors studied the rearrangements of the T-cell receptor beta--chain (C beta) and gamma-chain (J gamma) genes and immunoglobulin heavy (JH)- and light (C kappa, C lambda)- chain genes. An unique JH and C kappa gene rearrangement was found in the blood and spleen, whereas C beta and J gamma gene rearrangements were present in the blood, not in the spleen. Under alpha 2-IFN treatment, the JH gene rearrangement fainted dramatically, in contrast to that of the C beta gene. The study of messenger RNA (mRNA) of the T cell receptor alpha and beta chains evidenced the 1.3-kilobase (kb) and 1.6-kb bands in the blood and their absence in the spleen. The patient was human T-cell leukemia virus (HTLV)-II negative by Southern analysis of blood and spleen cells. It is concluded that the LGL expansion was clonal and not reactive to the HCL. Although the authors cannot definitely exclude that both HC and LGL proliferations stem in a common leukemic precursor, their findings support an association of the two entities.

Summary. A and A1 antigen were detected on human blood erythrocytes by immunoelectron microscopy using peroxidase‐conjugated antibodies. Cells were obtained from various normal A subgroups, including rare weak A phenotypes and infant (cord blood) samples. Erythrocytes were fixed prior to incubation with specific reagents. The detection of surface antigens was carried out by an indirect method involving anti‐A and anti‐A1 antibodies and conjugated anti‐immunoglobulin antibodies. The surface labelling was seen as a diffuse dense layer. Haem peroxidase‐like activity resulted in a faint background which did not interfere at the level of ultrathin sections, with surface staining due to exogeneous peroxidase. The most significant finding was the existence, in a given sample, of several populations of cells as revealed by their antibody‐binding capacity. The distribution of the various populations varied from one sample to another according to its subgroup. The progressive weakening of phenotype expression which characterizes the various subgroups from A1 to A weak was paralleled by a decreasing number of ‘antigen rich’cells, which were still detectable in weak phenotypes as a minor population. This study confirms that a given normal phenotype in fact represents a mixture of antigenically different populations of erythrocytes.