[Chronic myelomonocytic leukemia--functional study of monocytic leukemia cells].
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Biomedical subjects
Publications and source records attributed to F Kawano.
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Twenty-nine cases of adult T-cell leukemia were classified into four types according to the clinical features and course: smoldering, chronic, crisis, and acute. Only 2 of 14 patients with the acute type responded to therapy. The four types showed apparent differences in clinical features, complications, and prognosis, suggesting the need for different therapeutic regimens. For smoldering and chronic cases, no chemotherapy is recommended. However, in crisis and acute cases, aggressive chemotherapy is necessary, although the acute type cases showed extremely poor prognosis despite the most aggressive chemotherapy.
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Adult T-cell leukemia-lymphoma (ATL) is a unique T-cell cancer first described in Japan. We estimate that more than 200 patients a year have been detected in Kyushu. The surface phenotype of ATL cells characterized by monoclonal antibodies is T3+, T4+, T8-, T11+, and Tac+. In all cases the serum is positive for anti-human T-cell leukemia (lymphotropic) virus (HTLV-I) antibodies and the ATL cells contain the proviral DNA of HTLV-I. Variations in the clinical features of atypical cases suggest a division of the spectrum of ATL into five types: acute (prototypic), chronic, smoldering, crisis, and lymphoma. Screening of the sera from healthy adults for presence of the anti-HTLV-I antibodies revealed that 3.6% of healthy individuals in Kumamoto Prefecture, which is located in the middle of Kyushu, were HTLV-I carriers. The percentage of positivity increased with age and was higher in females than in males. It varied from town to town, ranging from 0 to 17.6%. Family studies showed that the routes of natural infection of HTLV-I are from mother to child and also from husband to wife. The third route is blood transfusion. The borderline between the healthy carrier state and smoldering ATL remains unclear. In the endemic areas smoldering ATL is frequently diagnosed in patients with fungus infection of the skin, chronic lymphadenopathy, interstitial pneumonitis, chronic renal failure, and strongyloidiasis. In addition our experiences with a concurrence of lymphoma-type ATL in three sisters and spontaneous remissions in a patient with chronic ATL are cited.
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Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder, differentiated from chronic myelogenous leukemia by several features. A case of CNL which was found by long-term culture to involve the Philadelphia chromosome is reported.
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A chromosome study was performed in 18 patients with adult T cell leukemia (ATL), who were divided into three groups according to their clinical manifestations: nine had acute ATL, six had chronic ATL, and three had smoldering ATL. Mitotic cells were obtained from peripheral blood, lymph node, or bone marrow and were analyzed by the G-banding technique. In acute ATL, the chromosome number ranged from diploid or pseudodiploid to hyperdiploid; in the chronic type, from hypodiploid to hyperdiploid; but in the smoldering type, it was diploid. Eight of nine patients with acute ATL had trisomy 3 and/or trisomy 7, whereas none of those with chronic ATL exhibited these aberrations. Patients with smoldering ATL had a normal karyotype. The present findings indicate that the more aggressive the clinical course of ATL, the more complex the numerical and structural chromosome abnormality.
Natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) were studied by routine methods in 11 patients with untreated malignant monoclonal gammopathy. NK and/or ADCC activity was clearly reduced in three patients with advanced disease. Moreover, sera from some myeloma patients impaired the ADCC and NK activity. A large quantity of purified monoclonal IgG from one patient appeared to inhibit NK and ADCC activity as did high concentrations of pooled polyclonal immunoglobulin from healthy persons. In two of these 11 patients, other malignancies were diagnosed prior to chemotherapy. One of these patients, who had nonsecretory myeloma, had marked impairment of NK and ADCC activity; the other, with IgG myeloma, had normal NK and ADCC activity.
Two siblings who developed adult T-cell leukemia (ATL) with unusual clinical courses are presented. The brother showed spontaneous remissions at the beginning stage of the disease of 6 years' duration, and the sister remains free of complaints for 6 years without chemotherapy. The patients and 2 of 12 healthy members of their family examined had serum antibodies against ATL-associated antigens (ATLA). The expression of ATLA was observed in the cultured lymphocytes from the patients and one of the family members.
We screened serum samples from patients with various hematological disorders and healthy individuals for the presence of adult T-cell leukemia/lymphoma associated antigen (anti-ATLA) antibodies. These antibodies were detected not only in all patients with ATL but frequently in those diagnosed as T-cell malignant lymphoma or T-cell chronic lymphocytic leukemia; the positivity rate of anti-ATLA antibody was lower in B- and null-cell-type lymphoma, B-cell chronic lymphocytic leukemia, and multiple myeloma. Patients with aplastic anemia or acute leukemia who had received frequent and massive blood transfusions also possessed anti-ATLA antibodies. About 5.5% of the healthy individuals over 40 years of age in the endemic area (Kumamoto) were carriers. The rate of positivity gradually increased with age, and was higher in females than in males. In addition, the peripheral blood mono-nuclear cells and/or lymph node cells from patients with various hematological disorders, including ATL, were examined. The presence of human T-cell leukemia/lymphoma virus type I (HTLV-I) proviral DNA was confirmed in all patients with ATL and in some with T-cell-type malignant lymphomas. However, in HTLV-I carriers or other patients with hematological disorders without ATL, proviral DNA was not detected. In endemic areas, detection of proviral DNA is essential for the classification and diagnosis of T-cell malignancies.
Adult T cell leukemia virus (HTLV or ATLV) proviral DNA integrated in the cellular DNA was examined by a modified Southern blotting method in the peripheral blood mononuclear cells and/or lymph node cells from 61 patients with adult T cell leukemia (ATL) and other hematologic diseases. Serum antibodies against ATL-associated antigens (ATLA) were also examined. The presence of human T cell leukemia virus (HTLV) proviral DNA was confirmed in all 20 patients with overt ATL and in 3 patients with T cell malignant lymphoma, who were seropositive but did not show clinical features characteristic of prototypic ATL. However, it was not detected in 6 antibody-positive healthy individuals and 8 seropositive patients with various hematologic disorders. Thus, the detection of proviral DNA by the method described here seems to be useful for the diagnosis of ATL in the endemic area and may provide a powerful tool for the classification of T cell malignancies.
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