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Translocation t(15;19)(q13;p13.1) defines a lethal midline carcinoma arising adjacent to respiratory tract in young people. To characterize molecular alterations responsible for the distinctly aggressive biological behavior of this cancer, we mapped the chromosome 15 and 19 translocation breakpoints by fluorescence in situ hybridization (FISH) and Southern blotting. To evaluate preliminarily the frequency, anatomical distribution, and histological features of t(15;19) cancer, we developed a FISH assay for paraffin sections. Our findings reveal a novel oncogenic mechanism in which the chromosome 19 translocation breakpoint interrupts the coding sequence of a bromodomain gene, BRD4. These studies implicate BRD4 as a potential partner in a t(15;19)-associated fusion oncogene. In addition, we localized the chromosome 15 breakpoint to a 9-kb region in each of two cases, thereby identifying several candidate oncogenes which might represent the BRD4 fusion partner. FISH evaluation of 13 pediatric carcinomas revealed t(15;19) in one of four sinonasal carcinomas, whereas this translocation was not detected in thymic (n = 3), mucoepidermoid (n = 3), laryngeal (n = 2), or nasopharyngeal (n = 1) carcinomas. Our studies shed light on the oncogenic mechanism underlying t(15;19) and provide further evidence that this highly lethal cancer arises from respiratory mucosa.

NALM-6-M1, one of eight leukemia cell lines cultured from the blood of a 19-year-old boy with non-T, non-B acute lymphoblastic leukemia (ALL) i n relapse, was characterized. This cell line was found t o be more than 90% cytoplasmic lmmunoglobulin positive (clg+) for both mu heavy and lambda light chains, but surface immunoglobulin (slg) and complement receptor (CR) negative. NALM-6-M1 was clg-for alpha, delta, and gamma heavy chains and kappa light chain. About

By means of the multiple marker analysis, a total of 55 human leukemia-lymphoma cell lines which included 15 T-cell, 30 B-cell, four myelomonocytic-cell, and six non-T, non-B cell lines was characterized for their marker profiles. The multiple markers used included a number of cell surface markers as detected by either rosette or immunofluorescence tests, enzyme assays, cytogenetic analysis, and certain functional assay. Based on the criteria previously defined it was found that all the cell lines were proved to represent original leukemia-lymphoma of ALL, AML, CLL, CML in blastic phase or variety of lymphomas. The monoclonality, a "frozen" state at a specific state of differentiation-maturation, and cytogenetic marker in each leukemia-lymphoma cell line were remarkable common properties and were stable for years of cultivation. Similar, if not identical, general characteristics were observed in the study on 344 cases of uncultured fresh leukemia-lymphomas by the multiple marker analysis. While no single marker specific to any type of tumor was found, the study offers not only a basis for better understanding of the biology of leukemia-lymphoma but also an insight into normal hematopoietic cell differentiation in man.

Expression of the cellular abl (c- abl ) oncogene was studied in K-562 and other chronic myelogenous leukemia (CML) cells and cell lines by means of Northern blot hybridization. In contrast to non-CML cells, which contained 7.4- and 6.8-kilobase abl -related transcripts, the CML cells contained a predominant and novel 8.2-kilobase abl -related RNA. In addition, the levels of abl -related message were up to eight times higher in CML cell lines from patients at the blast crisis stage of the disease compared with CML cells obtained during the chronic phase and with non-CML cells.

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A new hematopoietic cell line, designated KCL-22, was established in vitro by cultivation of pleural effusion cells obtained from a woman with chronic myelogenous leukemia in blast crisis. KCL-22 grew in suspension culture with a doubling time of 24 h and consisted of immature undifferentiated cells which were positive for periodic acid-Schiff and acid phosphatase staining. Chromosome analysis of the KCL-22 line showed a female karyotype with double Ph1 chromosomes and additional chromosome abnormalities. Its representative karyotype was 52,XX, + 1p-,+6,+8,+8,+8, t(9q+;22q-), +22q-. This cell line possessed receptors for the Fc portion of IgG, but lacked lymphoid cell characteristics and the Epstein-Barr virus-associated nuclear antigen. These results indicate that the KCL-22 cells were derived from chronic myelogenous leukemia cells. This cell line should prove useful for research involving various aspects of chronic myelogenous leukemia.