Michio Murata

Synergistic cytotoxic effect of quercetin and heat treatment in a lymphoid cell line (OZ) with low HSP70 expression

Heat shock protein 70 (HSP70) protects cells from various injurious stimuli and is important in cell growth and differentiation. However, its expression in leukemia cells has not been analyzed systematically. We, therefore, investigated the expression of HSP70 in various types of leukemia cells and hematopoietic cell lines. Immunoblot analysis revealed that HSP72/73 were expressed at low levels in the acute lymphocytic leukemia cells and lymphoid cell lines examined. However, heat (43 C for 2 h) preferentially augmented HSP72/73 expression in lymphoid cells. This induction was partially blocked by the treatment with quercetin (10 microM for 24 h). Finally, heat shock following quercetin treatment synergistically induced apoptosis in a lymphoid cell line (OZ). These observations suggest the possibility of selective purging of lymphocytic leukemia cells by combination with quercetin and heat.

Hodgkin's disease and Sjögren's syndrome

To the editor: It is well known that B-cell lymphoma is an occasional complication of Sjogren’s syndrome (SS) (13). Hyperimmune reaction has been assumed to play an important role in its lymphomagenesis. In contrast, there have been few reports on a causal association between Hodgkin’s disease (HD) and SS. Recently, Martin-Santos et al. reported a case of HD in a patient with primary S S and suggested that S S increases the risk of HD as well as non-Hodgkin’s lymphoma (NHL); however, the precise pathogenesis was unclear (4). In this paper we also describe a patient with SS who developed HD, and discuss the possible pathogenesis of these two disorders. The patient, a 69-year-old Japanese woman, was first admitted to our hospital because of left herniplegia in 1988. She also had a 4-yr history of keratoconjunctivitis sicca that required treatment with methylcellulose eye drops. Physical examination on admission revealed spastic paralysis of the left upper and lower extremities. Brain computed tomography showed a right putaminal hemorrhage. Abdominal sonography showed mild splenomegaly, but no nodular lesion was observed. Hematologic studies revealed a hemoglobin level of 12 g/dl, a leukocyte count of 2500/p1 and a platelet count of 8.7 x 104/pl. The total plasma protein level was 7.4g/dl, with a slight increase in the gammaglobulin fraction (23 %). Immunoglobulin concentrations were IgG, 1970 mg/ dl; IgA, 520 mg/dl; and IgM, 160 mg/dl. Antinuclear antibody (ANA) was positive at a dilution of 1:80. Serological tests were positive for rheumatoid factor (RF) and anti-SS-A, but negative for anti-SS-B antibody. Examination by an ophthalmologist showed diminished tear production (Shirmer tear test 3 mm for the right eye and 5 mm for the left eye) and punctate keratitis on rose bengal testing. Lip biopsy showed focal infiltratian of mononuclear cells and mild fibrosis, predominantly periductal in distribution (Fig. 1A). The patient was diagnosed as having SS. She remained &ell with symptomatic treatment until April 1992, when she noticed swelling of the right neck lymph node. Examination revealed hepatosplenomegaly with the spleen palpable 5 cm below the left costal margin. Abdominal computed tomography revealed a nodular lesion in the upper portion of the spleen. X-ray examination of the chest showed an enlarged right hilar lymph node and multiple nodular shadows in both lung fields. Laboratory examinations yielded the following results: total protein, 8.5 g/dl (gamma-globulin, 29%); IgG, 2700 mg/dl; IgA, 560 mg/dl; and IgM, 80 mg/dl. ANA and RF were negative. A biopsy specimen obtained from the right neck lymph node showed the presence of typical Reed-Sternberg (RS) cells with loss of the normal architecture of the node (Fig. 1B). The patient was diagnosed as having HD of mixed cellularity. Combination chemotherapy consisting of vincristine, cyclophosphamide and prednisolone resulted in considerable improvement of the splenomegaly and the chest radiograph abnormalities. Since Talal’s report, many studies have emphasized the correlation between SS and the development of NHL (1-3) Many theories have been proposed to account for this association, including exposure to radiation, previous cytotoxic chemotherapy, genetic predisposition, and intense antigenic stimulation (1-3). The fact that most of these lymphomas are derived from B lymphocytes may support the hypothesis that a chronic state of immunological hyperactivity is responsible for the malignant transformation (3). Although a few cases of patients with T-cell lymphoma and SS have recently been reported (5 , 6),fhe development of HD is rare. Since our patient did not have a history of either irradiation or immunosuppressive chemotherapy before the development of HD, a hyperimmune reaction of SS may have played a role in its pathogenesis. RS cells are pathognomonic of H D and are considered to be the neoplastic population in this disease. The cellular origin and nature of H D are still obscure; however, molecular genetic analysis had demonstrated clonal lymphocyte populations in many patients with H D (7-lo), supporting the concept that H D is a lymphocytic disorder. Meanwhile, recent studies have detected Epstein-Barr virus (EBV) DNA (10, 11) and mRNA (12) in RS cells, suggesting that EBV may be the transforming agent in some cases of HD. Interestingly, Miyasaka et al. reported that

TRANSLOCATION (3;21)(q26–2;q22–1) FOUND IN A PATIENT WITH MYELODYSPLASTIC SYNDROME AND LONG‐TERM EXPOSURE TO ORGANIC SOLVENTS

American Medical Association (1985) Current status of therapeutic plasmapheresis and related techniques. Report of the American Medical Association Panel on Therapeutic Plasmapheresis. /ournu1 of the American Medical Association, 253, 819. Bazarbashi, M.S., Smith, M.R., Karanes, C., Zielinski, I . & Bishop, C.R. (1 991) Successful management of Ph chromosome chronic myelogenous leukemia with leukapheresis during pregnancy. American journal of Hematology, 38, 235-237. Calabresi, P. & Chabner, B.A. (1991) Antineoplastic agents. The Pharmacological Basis of Therapeutics (ed. by A. Goodman Gilman, T. W. Rall, A. S. Nies and P. Taylor), p. 1209. Pergamon Press, New York. Gisslinger. H., Linkesch, W., Ludvig. H., Schott, A,. Fritz. E. & Radaszkiewicz. T. (1989) Long-term interferon therapy for thrombocytosis in myeloproliferative diseases. Lancet, i, 634-6 3 7. Gresser. I. (1982) Can interferon induce disease? Interferon 1982. Vol. 4 (ed. by I. Gresser). p. 95. Academic Press, London. Juarez, S.. Cuadrado-Pastor, J.M., Feliu. J.. Gonzalez-Baron. M., Ordonez, A. & Montero, J.M. (1988) Association of leukemia and pregnancy: clinical and obstetric aspects. American Journal of Clinical Oncology, 11, 159-165. Miller, J.B. (1976) Chronic myelocytic leukemia and the myeloproliferative diseases during the child-bearing years. Journal of Reproductive Medicine, 17, 2 1 7-224. Talpaz, M.. Kantarjian, H.M., McCredie. K., Keating. M.J.. Trujillo, J.M. & Guttermann, J.U. (1987) Clinical investigation of human alpha interferon in chronic myelogenous leukemia. Blood, 69,

Acute myelocytic leukemia associated with thrombocytosis and INV 3(q21.3; q26.2) in a case of Grönbland—Strandberg syndrome

Grönbland-Strandberg syndrome is an inherited connective tissue disorder with cutaneous, ophthalmologic, and systemic manifestations. Here we report a case of AML with thrombocytosis arising in a patient with this syndrome. Karyotypic analysis of bone marrow cells revealed the inversion 3 (q21.3;q26.2). To our knowledge, this is the first report of the association of AML with thrombocytosis and Grönbland-Strandberg syndrome. This might be a coincidental association, but it suggests some interesting speculations regarding the pathogenesis of these diseases.

Unbalanced translocation (1;7) and inversion 16 in a patient with acute myelocytic leukemia

Pericentric inversion of chromosome 16 has been delineated as a characteristic chromosome abnormality of acute myelomonocytic leukemia with abnormal eosinophils and a favorable prognosis. By contrast, unbalanced translocation (1;7) has been reported as frequently associated with therapy-related leukemia, and patients with this karyotypic abnormality are susceptible to severe infections which lead to a poor prognosis. Here we report the first case of acute myelocytic leukemia in which the complexed chromosomal aberrations of der(7)t(1;7)(cen;cen) and inv(16) were found simultaneously in the patients leukemia cells. Eosinocytosis has not been observed so far, but life-threatening pneumonia developed during the remission induction therapy.