We have studied a translocation, t(9;14) (pl3;q32), in a diffuse large-cell lymphoma cell line, KIS-1, that expresses the Ki-1 (CD30) antigen. Molecular cloning of the immunoglobulin heavy-chain locus (IGH) of this cell line revealed an unknown segment linked 5' to IGH. The breakpoint on chromosome 14 was 265 base pairs downstream from the 3' border of the JH6 joining gene segment. Class switch recombination deleted most of the constant genes of IGH (CH) and juxtaposed the Ca2 gene downstream of the translocation junction. Analysis of somatic cell hybrids and in situ chromosomal hybridization demonstrated that the translocated segment was normally located at band p13 of chromosome 9. The chromosome 9 sequences were transcriptionally active, giving rise to transcripts of =11 kilobases. The KIS-1 cells seemed to have a small quantity of chimeric transcripts containing both chromosome 9 and Ca2 sequences.A significant correlation has been observed between recurrent chromosomal translocations involving band 14q32, and the histologic and immunologic subtypes of human lymphoid malignancies (1)(2)(3). For example, the t(8;14)(q24;q32) is found in most cases of small-noncleaved-cell lymphoma, and the t(14;18)(q32;q21) is primarily associated with follicular small-cleaved-cell lymphoma. The lymphoma cells characterized by each of these translocations show B-cell immu-

A novel cell line, KM-H2, was established from the pleural effusion of a patient with Hodgkin's disease of mixed cellular type. Multiple phenotypic studies were carried out with this cell line. Acid phosphatase and nonspecific esterase activities were detected. Rosette formation with T lymphocytes and the receptors for C3b and Fc portion of IgG were positive. Among the antigens tested with a total of 22 monoclonal antibodies defining hematopoietic cell subsets or lineages, Ki-1, Leu-M1, MCS1, HLA-DR, and OKT9 antigens were found to be positive. The other antigens reportedly specific for T cells, B cells, natural killer (NK) cells, monocytes, interdigitating reticulum (IR) cells and dendritic reticulum cells were negative. These phenotypic features were identical to those of the Sternberg-Reed (SR) and Hodgkin (H) cells in the fresh materials reported by other researchers. Moreover, the KM-H2 cells and the parental pleural effusion cells shared several structural chromosome anomalies. These findings indicated that the KM-H2 cells are derived from the SR and H cells. Molecular genetic analysis of the KM-H2 cells disclosed that the human immunoglobulin JH gene was rearranged but not the JK gene, and that the human T cell receptor beta chain gene was of the germline type. Based on these properties of the KM-H2 cells, Hodgkin's disease may be derived from a cell lineage other than T cell or B cell.

A patient with large granular lymphocyte (LGL) leukemia that transformed into an acute or aggressive form after 20 months of the chronic phase is reported. The patient's leukemic cells were mature, medium-sized lymphocytes with sparse azurophil granules and the surface phenotypes of the cells were CD2+, CD3-, CD11+, and CD16+. Molecular analysis showed a germ line configuration in both T-cell receptor beta-chain genes and T-cell receptor tau-chain genes. A clonal anomaly of chromosome (trisomy 8) was demonstrated in peripheral blood cells. LGL after acute transformation of the disease displayed large blastic morphology with prominent nucleoli, intense basophilic cytoplasm, and numerous granules. Karyotypic analysis demonstrated a mosaic of trisomy 8 and trisomy 8 with an additional marker chromosome. Thus, transformation of chronic LGL leukemia into an acute or aggressive form in this patient was associated with morphologic and karyotypic changes of the leukemic cells. Patients with a stable form of chronic LGL leukemia should be examined carefully for the possible acute crisis associated with a clonal evolution.

A novel cell line, designated KIS‐1, was established from a patient with Ki‐1‐positive diffuse large cell lymphoma. Multiple phenotypic analysis of the KIS‐1 cells was carried out with a total of 22 monoclonal antibodies defining hematopoietic cell subsets and lineages. The KIS‐1 cells were positive for Ki‐1, B4, HLA‐DR, and 2D1 (common leucocyte) antigens, but were negative for the antigens reportedly specific for T cells, natural killer cells, granulocytes, monocytes, interdigitating reticulum cells and dendritic reticulum cells. The genomic analysis of the KIS‐1 cells showed not only the rearrangement of JH and Jk genes but also the probable rearrangement of Cγ genes. Moreover, the cells produced immunoglobulin γ chains. Thus, KIS‐1 was considered to be of B‐cell lineage. The lymphoma‐cell derivation of KIS‐1 was based on the following facts. The cytochemical, immunologic, cytogenetic properties and the results of the molecular genomic analysis in the KIS‐1 cells were essentially the same as those of the original tumor cells, and the KIS‐1 cells were negative for Epstein‐Barr virus‐associated nuclear antigen. KIS‐1 is the only known B‐cell line derived from Ki‐1‐positive diffuse large cell lymphoma, and should be useful for defining the biological implications of Ki‐1 antigen.

The morbidity and mortality of disease vary according to the region and may also change over time. The morbidity and mortality of malignant lymphoma are also affected by differences in ethnicity, lifestyle habits, geographical area, and time period. Increasing research on malignant lymphoma has focused on its pathophysiology, diagnosis, and therapeutic treatment. Recent improvements in the accuracy of clinical study, technologies such as next-generation sequencing, and the development of targeted molecular agents have also resulted in a number of excellent studies. This review summarizes the epidemiology of malignant lymphoma and highlights novel studies on adult T-cell leukemia/lymphoma recently published in Japan.