Lymphoblastic lymphoma of the pre-B phenotype with cutaneous presentation.

Lymphoblastic lymphoma (LBL) is a neoplasm of lymphoid precursors presenting usually as acute leukemia with bone marrow and peripheral blood involvement. Primary cutaneous involvement of LBL with a pre-B phenotype has to be considered an extremely uncommon occurrence, accounting for less than 1% of all non-Hodgkin lymphomas. A child with an LBL involving a single cutaneous manifestation of 6 months duration is presented. At the time of presentation, the lesion consisted of a rapidly enlarging deeply infiltrated tumor on the upper arm. Immunophenotypic analysis performed an paraffin-embedded and frozen tissue sections revealed 2 pre-B phenotype of the tumor cells. Similar results were obtained from lymph node and bone marrow biopsy specimens. After 26 months of polychemotherapy, the patient is currently in complete remission. We wish to add this case to the current literature of LBL with cutaneous involvement, emphasizing the importance of a correct diagnosis and the excellent response to the therapeutic regimen.

Treatment with 8-MOP and UVA enhances MHC class I synthesis in RMA cells: preliminary results.

The response of psoriasis and cutaneous T-cell lymphoma to treatment with 8-methoxypsoralen (8-MOP) and long wavelength ultraviolet light (UVA) is only partly understood. Psoralens form photoadducts within the DNA after activation by UVA and this damage leads to the inhibition of DNA synthesis. Additionally, it has been shown that different forms of DNA damage can induce a stress response, leading to upregulation of selected products. Among these are the major histocompatibility complex (MHC) class I genes. Thus the aim of the present study was to assess the rate of synthesis of MHC class I proteins in murine T-cell lymphoma cells (RMA) after treatment with 8-MOP and UVA. RMA cells were treated with 8-MOP (50-200 ng ml-1) and UVA (1 J.cm-2) and metabolically labelled with 35S-methionine 4 and 24 h after treatment. MHC class I synthesis was determined by immunoprecipitation of the cell lysates with an anti-Kb monoclonal antibody, Y3. After 4 h, treated and untreated cells demonstrated no differences in the rate of MHC class I synthesis. However, after 24 h a dose-dependent increase in MHC class I synthesis was observed. This increase in MHC class I expression could be responsible, at least partly, for the responses observed in patients treated with photopheresis.

Increased surface expression of class I MHC molecules on immunogenic cells derived from the xenogenization of P815 mastocytoma cells with 8-methoxypsoralen and long-wavelength ultraviolet radiation.

In a previous study we demonstrated that the treatment of the highly tumorigenic cell line, P815, with 8-methoxypsoralen and long-wavelength ultraviolet radiation resulted in the production of several immunogenic clones (tum-). Mice inoculated with the tum- cells survived much longer than mice inoculated with the original tumorigenic cells (tum+). It was suggested that the increased survival of mice treated with the tum- clones arose as a result of an increased antigenicity derived from the phototreatment. In this report we show that the tum- cells have a greater density of class I MHC molecules on their surface (50-157% compared to P815). Class I MHC density on the cell surface is required to elicit targeted cytotoxic responses. These results can be considered in terms of human class I MHC assays which show that many human tumor cells have a reduced expression of class I MHC. Because other DNA damaging agents have also been shown to enhance class I expression, it is suggested that in addition to the cytotoxic effects of these agents, other pleiotropic effects must be considered. Photochemotherapy may phenotypically alter cells so that the enhanced expression of class I MHC molecules on the surface of phototreated cells may be associated with the clinical responses observed in cutaneous T cell lymphoma patients.

Psoralen-protein photochemistry--a forgotten field.

8-Methoxypsoralen in combination with long wavelength ultraviolet light is employed for the treatment of several cutaneous disorders, such as psoriasis, vitiligo and mycosis fungoides. It is common to attribute the efficacy of the photochemotherapy to the formation of psoralen DNA photoadducts. Thus, the main research effort has been directed towards the elucidation of nucleic acid photochemistry and related subsequent events (mutagenicity, toxicity). However, psoralens have been shown to undergo photoaddition reactions with other cellular components. In this review the status of psoralen-DNA photobiology is briefly summarized. The main focus, however, is on a survey of psoralen photochemical modification of proteins and the ways by which these additional photobiological events can impact the antigenicity and potentially immunogenicity of treated cells. Some preliminary results show the extent of psoralen-amino acid photoadduct formation and their impact on enzymatic processing.

The specific effects of 8-methoxypsoralen photoadducts on cell growth: HPLC analysis of monoadduct and crosslink formation in cells exposed to split-dose treatment.

The effects of 8-methoxypsoralen (8-MOP) monoadducts and crosslinks on growth and viability of mastocytoma cells were investigated. To induce monoadduct formation (4',5'-monoadducts and 3,4-monoadducts), the cells were incubated with 8-MOP (1 microgram ml-1) and exposed to 419 nm radiation, resulting in the formation of more than 96% monoadducts. After washing and resuspension, the cells were exposed to a small dose of long-wavelength UV radiation (UVA, 2 J cm-2) to convert monoadducts into crosslinks. Similar adduct levels were obtained after either 8-MOP plus visible light treatment or 8-MOP plus split-dose protocol. Cells treated with 419 nm light resumed normal growth rates more rapidly than cells which also received the UVA dose. High performance liquid chromatography (HPLC) analysis of DNA obtained from each group of cells showed that the UVA step resulted in an increase in crosslinks from 3.2% after 419 nm radiation to 56.5% after UVA irradiation.