Tatsuhiko Amagasaki

Phenotypic diversity and prognosis of adult T-cell leukemia

We examined phenotypically 107 patients with adult T-cell leukemia (ATL), using a panel of monoclonal antibodies, in order to clarify the occurrence of aberrant phenotypes, and to determine the correlation between phenotypic diversity and prognosis. The incidence of the typical (CD4+.CD8-) phenotype, the double-negative (CD4-.CD8-), the double-positive (CD4+.CD8+), and the CD8-positive (CD4-.CD8+) phenotypes was 81%, 7%, 7%, and 4%, respectively. The median survival time (MST) for all patients was 10.0 months with 17% survival at 2 years. The patients with typical phenotypes had a 10.2 month MST with 20% survival at 2 years, significantly better than the patients with the unusual phenotypes whose MST were 4.9, 7.8, and 2.6 months, respectively, for the double-negative, double-positive, and CD8-positive phenotypes. Lack of antigens reactive with CD2, CD3, CD5, and WT31 monoclonal antibody panels was one factor in bad prognosis, but the presence of CD4 and CD8 antigen abnormalities was much more significant.

Frequency of eosinophilia in adult T‐cell leukemia/lymphoma

Cases of adult T‐cell leukemia/lymphoma (ATLL) display several peculiar clinical features, including skin rash, hypercalcemia, and an increase in the absolute neutrophil count. The patients rarely have pronounced eosinophilia. In this study, the eosinophilia observed in lymphoproliferative disorders of 62 patients with ATLL, 27 with T‐cell lymphoma (TL), and 19 with B‐cell lymphoma (BL) was investigated. The incidence of eosinophilia (⩾ 570/μl) was higher in patients with ATLL than in patients with TL or BL. Thirteen patients with ATLL (21.0%), 3 with TL (11.1%), and 2 with BL (10.5%) had eosinophilia. Of these patients, three with ATLL and one with TL who had a pathologic diagnosis of immunoblastic lymphadenopathy (IBL) showed pronounced eosinophilia up to 10,934/μl. Because the number of eosinophils in the peripheral blood of these patients correlated both with the number of ATLL cells and the degree of lymphadenopathy and because this fluctuated with chemotherapy, it seems likely that the secretion of some lymphokines by the lymphoma cells is responsible for the eosinophilia. Cancer 1992; 69:966–971.

Adult T cell leukemia with atypical surface phenotypes: clinical correlation.

The leukemic cells of 57 patients with adult T cell leukemia (ATL) were analyzed for their immunologic surface markers. Forty-four cases showed normal mature inducer/helper T cell phenotype (typical group: E-RFC+, Leu-1+, 2a-, 3a+ MASO36c-), but the other 13 cases showed unusual surface phenotypes (variant group) and could be subdivided into several groups (V1 to V5). Four cases had absent or low Leu-1 positivity (V1: E-RFC+, Leu-1-, 2a-, 3a+, MASO36c-), while two other cases with low Leu-1 positivity had both Leu-2a and 3a, a characteristic of cortical thymocytes, but were unreactive with MASO36c (V2: E-RFC+, Leu-1-, 2a+, 3a+, MASO36c-). Three cases lacked both Leu-2a and 3a despite having other T cell markers (V3: E-RFC+, Leu-1+, 2a-, 3a-, MASO36c-). The next three cases had low rosette-forming ability with sheep RBCs (V4: E-RFC-, Leu-1- approximately +, 2a- approximately +, 3a+, MASO36c-). Interestingly, one other case showed high reactivity against anti-Leu-7, which is believed to be one of the monoclonal antibodies directed against natural killer cells (V5: E-RFC+, Leu-1+, 2a-, 3a+, 7+, MASO36c-). Clinical and hematologic differences between the typical group and variant group were investigated, and it was found that the variant group (excluding V5) have statistically significant (P less than .002) higher serum lactic dehydrogenase (LDH) activity. The overall survival in the variant group was worse than in the typical group, but it was not quite statistically significant (P = .072). The median survival time was eight months for typical cases and only four months for variant cases; six cases died within two months. The V5 case was unusual not only because the patients leukemic cells have Leu-7 antigen but also because she survived more than nine years after initial diagnosis. There seems to be some correlation between phenotypic diversity of ATL cells and prognosis.

Prognostic significance of the proportion of Ki‐67‐positive cells in adult t‐cell leukemia

The authors examined peripheral blood samples from patients with adult T‐cell leukemia (ATL) using the monoclonal antibody Ki‐67 which detects a nuclear antigen present in actively proliferating cells. In patients with chronic ATL, the percentage of Ki‐67‐positive cells was significantly lower than in acute ATL patients (median values, 3.3% versus 18.9%, P < 0.001). Furthermore, there was a significant inverse correlation between the percentage of Ki‐67‐positive cells and the length of survival (P < 0.001). Serum lactic dehydrogenase (LDH) levels also showed a significant inverse correlation with survival, but this was less strong than that for Ki‐67 (0.01 < P < 0.02). Thus, Ki‐67 positivity appears to indicate the aggressiveness of ATL, and can possibly be used for the clinical classification of ATL patients as well as for the prediction of prognosis.

Adult T-cell leukemia with an unusual phenotype, Leu-2a positive and Leu-3a negative

SummaryA case of adult T-cell leukemia (ATL) with an unusual phenotype is presented. Leukemia cells of this patient reacted with anti-Leu-2a monoclonal antibody, although most of ATL cases are reported to show the phenotype of helper/inducer T-cell. It is indicated that the surface phenotype of ATL is rather heterogenous.

Detection of adult T‐Cell leukemia‐associated antigen in T‐Cell malignancies in the Nagasaki district of Japan

Adult T‐cell leukemia‐associated antigen (ATLA), a human retrovirus‐associated antigen, and anti‐ATLA antibodies were examined in 52 cases of T‐cell malignancies in the Nagasaki district in southwestern Japan, which is known to be an ATL endemic area. These T‐cell malignancies included 27 cases of ATL, 2 cases of T‐cell chronic lymphocytic leukemia (T‐CLL), 18 cases of T‐cell lymphoma, and 5 cases of mycosis fungoides. Using the immunofluorescence method, ATLA‐positive cells were detected in short‐term mass culture of mononuclear cells from 22 of the 27 ATL patients, both T‐CLL patients, 17 of 18 T‐cell lymphoma patients, and 3 of the 5 mycosis fungoides patients. In an ATL patient in whom a high percentage of ATLA‐positive cells were detected, many type C virus particles were observed in the extracellular space of the cultured mononuclear cells with an electron microscope. Sera from all 27 of the ATL patients, the 2 T‐CLL patients, 15 of the 18 T‐cell lymphoma patients, and 4 of the 5 mycosis fungoides patients were anti‐ATLA antibody positive. These results indicate the possible participation of the retrovirus, ATL virus (ATLV), in these T‐cell malignancies in ATL‐endemic areas.

Analyses of adult T-cell leukemia using the monoclonal (anti-Leu-1, anti-Leu-2a, and anti-Leu-3a) and heterologous anti-glycolipid (anti-asialo GM1) antibodies☆

Abstract We determined the surface phenotype of leukemic cells in adult T-cell leukemia (ATL) by immunofluorescence. Peripheral blood lymphocytes of 10 ATL patients were stained with monoclonal antibodies either directed to the surface antigens of all peripheral T cells (Leu-1), suppressor/cytotoxic (Leu-2a) T cells, or helper/inducer (Leu-3a) T cells. In addition, staining with the heterologous anti-glycolipid antiserum (anti-asialo GM1) was also examined. Cytofluorographic analyses revealed the absence of anti-Leu-2a and anti-asialo GM1-positive cell populations in all 10 cases of ATL studied. In contrast, the phenotypes of T-chronic lymphocyte leukemia cells were more variable from patient to patient. Morphological examination of fluorescence-activated cell sorter-separated Leu-1- or Leu-3a-reactive cells from ATL patients strongly suggested that the leukemic cells themselves expressed anti-Leu-1- and anti-Leu-3a-reactive antigens. From the above findings, we believe that these antibodies will be useful not only for the diagnosis of leukemia but also for the understanding of T-cell ontogeny and pathogenesis of leukemia in man.

T lymphomas associated with human T-cell leukemia-lymphoma virus may show phenotypic and functional differences from adult T-cell leukemias

We report phenotypic and functional characterization of lymph node cells from 27 patients with T lymphoma from the Nagasaki district of Japan. Nagasaki is one of several areas where adult T-cell leukemia is endemic, and sera from 18 of 23 patients examined (78.3%) were positive for antibody to adult T-cell leukemia-associated antigen. The majority of cases (24 of 27) showed the Leu-2a-, 3a+, MASO36c- phenotype similar to adult T-cell leukemia, but seemed to be subdivided into four groups according to the presence or absence of Leu-1 antigen and the receptor for sheep erythrocytes (SRBC). Eleven cases had both Leu-1 antigen and the receptor for SRBC (E-RFC+, Leu-1+, 2a-, 3a+), but 6 cases lacked Leu-1 antigen (E-RFC+, Leu-1-, 2a-, 3a+), 4 cases lacked receptors for SRBC (E-RFC-, Leu-1+, 2a-, 3a+), and 3 cases lacked both of these markers (E-RFC-, Leu-1-, 2a-, 3a+). The effects of lymph node T cells on pokeweed mitogen (PWM)-induced normal B-cell differentiation was studied in 10 cases. Lymph node T cells of 5 cases showed helper activity without any suppressor activity, and 2 cases showed suppressor activity with almost no detectable helper activity, similar to adult T-cell leukemia cells. Two other cases lacked particular functional effects. These results suggest the possibility that Leu-3a+ T-cell lymphoma may be functionally subdivided into at least two types, a helper type and a suppressor (adult T-cell leukemia) type.

Appearance time of leukemic cells with t(8;21) in bone marrow

A 30-year-old man was referred because of slight leukocytosis. The hematological findings, including those of the bone marrow, showed no evidence of leukemia. The level of neutrophil alkaline phosphatase (NAP) in the peripheral blood was normal, as were the chromosomes from bone marrow cells. Fifteen months later, the disease was diagnosed as M2 (according to the French-American-British classification) showing a t(8;21)(q22;q22) and a low NAP level as two markers of M2 cells. This is probably the first case of acute leukemia in which the cytogenetic analysis was performed before and after the appearance of a specific chromosome abnormality.