Acute Adult T-cell Leukemia Research Articles

Adult T‐cell Leukemia in Spouses

A married couple who developed adult T‐cell leukemia (ATL) is described. The husband presented with acute ATL and died soon after admission in spite of aggressive chemotherapy, and his wife, who is diagnosed as smoldering ATL, has been followed in the out‐patient clinic. The couple had serum antibodies against human T‐cell leukemia virus type I (MTLV‐I) and the monoclonal integration of HTLV‐I proviral DNA in their lymphocytes. The patients described represent the first reported example of ATL in a married couple.

Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease

Serum concentrations of soluble interleukin 2 receptors (sIL 2R) were measured by an enzyme-linked immunosorbent assay (ELISA) in 30 patients with adult T cell leukemia (ATL), in 9 patients with other hematopoietic malignancies, and in 17 asymptomatic individuals seropositive for human T cell leukemia virus type I (HTLV-I). Sixty HTLV-I seronegative, age-matched controls showed a normal range of form 63.2 to 480.8 U/mL. All asymptomatic carriers of HTLV-I had sIL 2R in their sera within the normal range. sIL 2R in sera was not related to the anti-HTLV-I antibody titer. Eleven patients with acute ATL, a clinical phenotype with median survival rate of 4.4 months, had markedly elevated sIL 2R (11,100 to 99,000 U/mL), but eight patients with smoldering ATL had low sIL 2R values (less than 480.8 U/mL) comparable to controls. Eleven patients with chronic ATL had intermediate elevated levels of sIL 2R (480.8 to 37,300.0 U/mL). Serum levels of sIL 2R correlated with the number of ATL cells (r = 0.812) and CD25-positive cells (r = 0.725) circulating in the peripheral blood. Longitudinal studies performed in four patients with ATL showed significant correlation between serum concentration of sIL 2R and activity of the malignancy. These findings suggest that the level of sIL 2R in serum indicated tumor load and, possibly, prognosis.

Soluble Interleukin 2 Receptors in Sera of Japanese Patients With Adult T Cell Leukemia Mark Activity of Disease

Serum concentrations of soluble interleukin 2 receptors (sIL 2R) were measured by an enzyme-linked immunosorbent assay (ELISA) in 30 patients with adult T cell leukemia (ATL), in 9 patients with other hematopoietic malignancies, and in 17 asymptomatic individuals seropositive for human T cell leukemia virus type I (HTLV-I). Sixty HTLV-I seronegative, age-matched controls showed a normal range of form 63.2 to 480.8 U/mL. All asymptomatic carriers of HTLV-I had sIL 2R in their sera within the normal range. sIL 2R in sera was not related to the anti-HTLV-I antibody titer. Eleven patients with acute ATL, a clinical phenotype with median survival rate of 4.4 months, had markedly elevated sIL 2R (11,100 to 99,000 U/mL), but eight patients with smoldering ATL had low sIL 2R values (less than 480.8 U/mL) comparable to controls. Eleven patients with chronic ATL had intermediate elevated levels of sIL 2R (480.8 to 37,300.0 U/mL). Serum levels of sIL 2R correlated with the number of ATL cells (r = 0.812) and CD25-positive cells (r = 0.725) circulating in the peripheral blood. Longitudinal studies performed in four patients with ATL showed significant correlation between serum concentration of sIL 2R and activity of the malignancy. These findings suggest that the level of sIL 2R in serum indicated tumor load and, possibly, prognosis.

Clinical Study on the Serum Levels of Immunosuppressive Acidic Protein in Patients with Adult T-Cell Leukemia

Serum levels of immunosuppressive acidic protein (IAP) were measured in patients with adult T-cell leukemia (ATL) in order to clarify its significance in this disease. The mean levels in patients with both acute (854 +/- 404 micrograms/ml) and chronic ATL (439 +/- 103 micrograms/ml) were significantly higher than in sera of healthy controls (367 +/- 104 micrograms/ml). However, mean levels in patients with smoldering ATL, healthy T-cell lymphotropic virus type 1 (HTLV-1) carriers and healthy controls showed no differences. Levels in crisis in chronic and smoldering ATL were similar to those in patients with acute ATL. Serial measurements of serum IAP in a number of patients revealed that the levels reflected each patient's clinical course, suggesting a potential for use in evaluating the effects of chemotherapy.

Significance of chromosome 14 anomaly at band 14q11 in Japanese patients with adult T-cell leukemia.

The chromosomes of leukemic blood cells in eight Japanese patients with acute adult T-cell leukemia (ATL) were examined by a direct method or short-term culture method without any mitogens. Six patients showed a chromosome 14 anomaly with a break at band q11-13: inv(14)(q11q32) in two patients, t(11;14)(p13;q13) in one patient, t(14;14)(q11;q32) in addition to del(14)(q11q13) in another, and only del(14)(q11q13) in two patients. Thus, a proximal 14q rearrangement exists in ATL as in other types of T-cell malignancies. Based on these facts, the pathogenesis of ATL is discussed in reference to the literature.

Origin of human T-lymphotrophic virus I-positive T cell lines in adult T cell leukemia. Analysis of T cell receptor gene rearrangement.

Using the clone-specific rearrangement of the T cell receptor gene as the genetic marker of the clonotype, we analyzed the clonal origin of the interleukin 2 (IL-2)-dependent human T-lymphotrophic virus I (HTLV-I)-positive T cell lines established from various adult T cell leukemia (ATL) patients. From a patient with chronic ATL, whose leukemic cells proliferated in vitro in response to IL-2, we repeatedly established leukemic T cell clones having the same rearrangement profile of the T beta chain gene as the leukemic cells. By contrast, established cell lines from acute ATL patients had different beta chain gene rearrangements from those of the leukemic cells. These HTLV-I+ T cell lines might not be the direct progeny of the leukemic cells, but that of T cells infected either in vivo or in vitro. These IL-2-reactive nonleukemic T cells might have been selected in vitro, because their leukemic cells failed to respond to IL-2, despite the expression of IL-2 receptor. The analysis of the T cell receptor gene rearrangement may give a new approach for the elucidation of the mechanism of leukemogenesis and the origin of the HTLV-I+ T cell lines in ATL.

Natural Antibodies in Sera From Japanese Individuals Infected With HTLV-I Do Not Recognize HTLV-III

AbstractSeventy-one sera from Japanese individuals infected with human T cell leukemia virus type I (HTLV-I) were examined for the presence of antibodies to HTLV-III by an enzyme-linked immunosorbent assay (ELISA) and by a strip radioimmunoassay based on the Western blot technique. The sera were from 23 healthy carriers and from 48 patients, including 18 with smoldering adult T cell leukemia (ATL), 13 with chronic ATL, and 17 with acute ATL. All people tested lived in the southwestern part of Japan, a known endemic area for HTLV-I infection. Antibodies against HTLV-I were detected in all sera both by indirect immunofluorescent methods and strip radioimmunoassay using cell lysates. Six sera were reactive in the ELISA assay for HTLV-III. But these sera did not react specifically to HTLV-III-related proteins (p15, p24, gp41) when analyzed by strip radioimmunoassay. Our data suggest that coincidental infection of HTLV-I and HTLV-III is quite rare in Japan.

Natural antibodies in sera from Japanese individuals infected with HTLV- I do not recognize HTLV-III

Seventy-one sera from Japanese individuals infected with human T cell leukemia virus type I (HTLV-I) were examined for the presence of antibodies to HTLV-III by an enzyme-linked immunosorbent assay (ELISA) and by a strip radioimmunoassay based on the Western blot technique. The sera were from 23 healthy carriers and from 48 patients, including 18 with smoldering adult T cell leukemia (ATL), 13 with chronic ATL, and 17 with acute ATL. All people tested lived in the southwestern part of Japan, a known endemic area for HTLV-I infection. Antibodies against HTLV-I were detected in all sera both by indirect immunofluorescent methods and strip radioimmunoassay using cell lysates. Six sera were reactive in the ELISA assay for HTLV-III. But these sera did not react specifically to HTLV-III-related proteins (p15, p24, gp41) when analyzed by strip radioimmunoassay. Our data suggest that coincidental infection of HTLV-I and HTLV-III is quite rare in Japan.

Adenosine deaminase in plasma of patients with adult T-cell leukemia (ATL): correlation between enzyme activity and the ATL subtypes.

Adenosine deaminase (ADA) was assayed in plasma from 14 patients with adult T-cell leukemia (ATL) (eight with acute ATL and six with smoldering or chronic ATL), 20 male family members (ten were anti-ATLA antibody positive and the other ten negative), and 25 normal individuals. ADA activity was uniformly higher in plasma from patients with ATL than normal controls. This enzyme activity significantly increased in acute ATL in comparison to smoldering or chronic ATL. In families of ATL patients, no statistical difference in ADA activity between the anti-ATLA antibody-positive group and -negative group could be discerned. The enzyme activity in a patient with acute ATL, after a bone-marrow transplant, rapidly increased as leukemic cells increased in peripheral blood. These findings indicate that the levels of ADA activities in plasma from ATL patients reflect the condition of this disease. Thus, measurement of this enzyme activity offers a further parameter to distinguish subtypes of ATL, and is of prognostic and therapeutic value.

Chromosomal Aberrations in Adult T Cell Leukemia: Relationship to the Clinical Severity

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.

Chromosomal aberrations in adult T cell leukemia: relationship to the clinical severity

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.

Epidemiologic and immunologic characteristics of acute lymphoblastic leukaemia and adult T-cell leukaemia in Japan

Epidemiologic and immunologic characteristics of acute lymphoblastic leukaemia and adult T-cell leukaemia in Japan

Clinical features of OKT4+/OKT8+ adult T-cell leukemia

Adult T-cell leukemia (ATL) has a range of clinical characteristics. Phenotypically the leukemic cells usually express the helper/inducer associated antigen OKT4 with lack of OKT8. We have observed three patients with acute ATL cytologically indistinguishable from OKT4+/OKT8− ATL but whose neoplastic cells had the unusual phenotype, OKT3+, OKT4+, OKT6−, OKT8+ OKT9+/−, OKT11−, Tac+/−, TdT−. All patients had abnormal karyotypes and antibodies against anti-ATL associated antigens as well as proviral DNA of human T-cell leukemia virus in the leukemic cells. The clinical course was complicated by skin eruptions, hypercalcemia, pulmonary infection and disseminated intravascular coagulopathy. All died of complications shortly after diagnosis. The clinical features of these patients were similar to those of OKT4+/OKT8− ATL. However, their acute course suggests that co-expression surface antigens OKT4 and OKT8 may be a sign of aggressive nature of the disease with poor prognosis.