Hidehisa Kohno

PRIMARY GASTRIC T-CELL LYMPHOMA WITH MANIFOLD HISTOLOGIC APPEARANCES

A rare case of malignant T‐cell lymphoma with manifold histologic appearances was described. The lymphoma occurred in the stomach of a 50‐year‐old Japanese male. Grossly, the lymphoma exhibited a deeply ulcerated mass. Histologically, in addition to diffuse infiltrate of large lymphoid cells with deeply indented nuclei, there were many epithelioid cell granulomas, remarkable tissue eosinophilia and stromal fibrosis, mimicking inflammatory disease. Immunohistochemical studies and a gene analysis demonstrated the T‐cell phenotype.

Adult T cell leukemia associated with eosinophilia: analysis of eosinophil-stimulating factors produced by leukemic cells.

The mechanism of eosinophilia in a patient with adult T cell leukemia (ATL) was investigated. A 61-year-old woman with ATL presented marked eosinophilia. No parasite infections or allergic diseases were found in this patient. The number of eosinophils fluctuated in parallel with that of ATL cells during her clinical course. The patients serum and the culture supernatant of ATL cells showed eosinophil colony-stimulating activity. Northern blot analysis of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5), which are known eosinophil CSFs, showed that only GM-CSF but not IL-3 or IL-5 was expressed in freshly separated and cultured ATL cells. Since neutrophil and monocyte numbers did not increase, it is suggested that GM-CSF and unknown cytokines other than IL-3 and IL-5 produced by ATL cells synergistically stimulated eosinophil precursors in the present case.

CD20-positive adult T-cell leukemia.

A 67‐year‐old woman was admitted to our hospital because of lymphadenopathy and lymphocytosis. Monoclonal integration of HTLV‐I provirus DNA was detected, and a diagnosis of adult T‐cell leukemia (ATL) was made. Flow cytometry revealed that the ATL cells expressed CD20 as well as T‐cell‐associated antigens, and expression of CD20 mRNA was also demonstrated. A novel T‐cell subpopulation expressing CD20 molecules has recently been identified. This is the first report of CD20‐positive ATL, suggesting that HTLV‐I can infect and transform CD20‐positive T cells. Am. J. Hematol. 66:39–41, 2001.

Pathologic characteristics of human T-cell lymphotropic virus (HTLV)-related extranodal orofacial lymphomas

Eleven cases of extranodal orofacial lymphomas (EOFL), consisting of four HTLV-related and seven HTLV-unrelated EOFL, were investigated with respect to the immunohistochemical and clinical features. HTLV-related EOFL were of T-cell phenotype and were associated with a poorer prognosis than HTLV-unrelated EOFL, most of which were of B-cell origin. The appearance of giant cells with cerebriform nuclei was helpful in identifying HTLV-related EOFL. The relatively high incidence of T-cell type EOFL in our series was considered to be related to the high percentage of HTLV carriers in our district, an area endemic for adult T-cell leukemia-lymphoma.

Simultaneous establishment of myeloid and B‐lymphoid cell lines with identical chromosome abnormalities from Philadelphia chromosome‐positive chronic myelogenous leukaemia

Summary. Two continuously growing cell lines, designated YOS‐M and YOS‐B, were established simultaneously from a patient with Philadelphia (Ph1) chromosome‐positive chronic myelogenous leukaemia (CML) in myeloid blast crisis. Both YOS‐M and YOS‐B had the Ph1 chromosome and identical additional chromosome abnormalities, which were not detected in the chronic phase. Cytochemical analysis showed that YOS‐M was significantly positive for peroxidase, whereas YOS‐B was entirely negative. YOS‐M expressed myeloid‐associated antigens (CD14, CD33) as well as CD4, CD25 and CD34. The surface phenotype of YOS‐M was identical to that of the leukaemic blasts found in the patient. On the other hand, YOS‐B expressed mature B‐cell markers, CD19, CD20, CD21 and surface immunoglobulin, but not myeloid‐associated antigens. These two cell lines showed an identical rearrangement pattern of the break point cluster region on chromosome 22, but rearrangement of the immunoglobulin heavy chain gene was detected only in YOS‐B. These findings provide definite evidence that CML cells still have the capability to differentiate and mature along different haematopoietic cell lineages even after blast crisis.

Expression of theGfi-1 Gene in HTLV-I-Transformed T Cells

Human T-cell leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and immortalizes human T cells interleukin-2 (IL-2)-dependently in vitro. Protracted culture of HTLV-I-infected T cells enables them to grow IL-2-independently. Although acquisition of IL-2-independent growth has been correlated with activation of signal transducers and activators of transcription (STATs), the precise mechanism of IL-2-independent growth is unknown. We found that expression of theGfi-1 (growth factor independence-1) gene was elevated in most HTLV-I-transformed IL-2-independent cell lines but in few HTLV-I-infected IL-2-dependent cell lines.We also found elevated expression ofGfi-1 in fresh leukemic cells of ATLL patients.Although expression ofGfi-1 is correlated with activation of STAT3, induction of the dominant negative form of STAT3 in the HUT102 cell line does not alter the level ofGfi-1 expression. Furthermore, MT2 cells treated with Gfi-1 antisense oligonucleotide had reduced [3H]thymidine uptake compared with MT2 cells treated with Gfi-1 sense oligonucleotide. These findings indicate thatGfi-1 activation is involved in the IL-2-independent growth of HTLV-I-transformed T cells in vitro and in the development of ATLL in vivo, but is not induced by STAT activation.