Plasma cell leukemia 3 months after autologous blood cell transplantation for multiple myeloma.

We describe a patient with multiple myeloma who was treated with intensive therapy and autologous blood cell transplantation as her first-line treatment. The disease relapsed 3 months after the transplant as plasma cell leukemia and the patient succumbed in 4 weeks. We suggest that an aggressive plasma cell clone may be selected during the course of intensive treatment. Complex karyotypic findings are also presented.

Sublethal damage repair after fractionated irradiation in endometrial cancer cell lines tested with the 96-well plate clonogenic assay.

Two long-established and seven newly established endometrial adenocarcinoma cell lines were tested for their capacity to repair sublethal damage after fractionated irradiation. Cell survival was determined with the 96-well plate clonogenic assay based on limiting dilutions. Total radiation doses of 0.75 Gy, 1.25 Gy, 2.50 Gy, 5.00 Gy and 7.50 Gy were used either as a single dose or divided into two or three equal fractions with a 24 h interval. Survival data were fitted to the linear quadratic model, and the area under the survival curve (AUC), equivalent to the mean inactivation dose, was obtained with numerical integration. The amount of sublethal damage repair (SLDR) was expressed as an area-under-the-curve (AUC) ratio comparing survivals from fractionated-dose with those from single-dose experiments. SLDR capacity of the cell lines expressed as an AUC ratio varied between 1.00 and 1.59, and the mean was 1.17. Two highly radiosensitive cell lines were found to be SLDR-deficient, but most of the cell lines studied had some SLDR capacity. We have earlier shown that endometrial cancer cell lines as a group are more radiosensitive than squamous-cell carcinoma (SCC) lines. Data obtained in this study suggest that the capacity for SLDR in these cell lines is rather limited compared with the majority of SCC lines tested. This finding underlines further the high radioresponsiveness of endometrial cancer.

Effects of radiation fractionation on four squamous cell carcinoma lines with dissimilar inherent radiation sensitivity.

The effect of radiation fractionation was investigated using a new 96-well-plate clonogenic assay in four squamous cell carcinoma lines. Earlier experiments had shown that two of the cell lines (UT-SCC-1A and UM-SCC-14A) were inherently relatively sensitive to irradiation, and two (UM-SCC-1 and UM-SCV-1A) relatively resistant. All of the four carcinomas from which the cell lines were established had poor clinical outcome. The radiation doses were given as a single exposure, or split into two or three equal fractions with a 24-h interval. The two inherently sensitive cell lines showed enhanced survival after radiation fractionation as compared with a single dose, whereas the resistant cell lines did not. The result suggests that both the inherent resistance of cancer cells to irradiation and the repair of sublethal radiation damage may lead to treatment failure, and that shortening of the total irradiation time may overcome cancer cell recovery between fractions in some, but not in all carcinomas.

Comparison of DNA and karyotype aneuploidy in malignant lymphomas.

Tumors from 48 patients with non-Hodgkin's lymphoma were examined for flow cytometric DNA ploidy and chromosome constitution to determine the degree of concordance of these two methods. Histologically, there were 24 low-grade, 19 intermediate, and 5 high-grade lymphomas. Flow cytometry revealed an aneuploid cell population in 19% of the cases. The mean DNA index of the aneuploid tumors was 1.58 +/- 0.71. The frequency of DNA aneuploidy was only slightly higher (23%) in intermediate than in low-grade lymphomas (17%). None of the five high-grade lymphomas showed DNA aneuploidy. The chromosome study was successful in 81% of cases (39 of 48), and clonal chromosome abnormalities were observed in 92% of these (36 of 39). In most of the chromosomally abnormal clones the chromosome number was in the diploid range. Most tumors with pseudodiploid (46 chromosomes), hypodiploid (45-44 chromosomes), or hyperdiploid (47-49 chromosomes) clones were DNA diploid by flow cytometry. On the other hand, all specimens with a chromosome number exceeding 50 were DNA aneuploid by flow cytometry. Therefore, flow cytometric DNA analysis appears to be a rather coarse method that will detect aneuploidy only when there is a major increase in chromosome material.

t(2;5) (p23;q35)-A Specific Chromosome Abnormality in Large Cell Anaplastic (Ki-1) Lymphoma.

Chromosome abnormalities of three patients with Ki-1 lymphoma are presented. In order to be included in the study each case fulfilled the following criteria: the majority of the tumour cells were positive for the Ki-1 antigen (CD30), and the cells were large with relatively abundant, slightly basophilic cytoplasm. In all cases, a major proportion of mitoses contained a complicated clonal chromosome abnormality. Two patients had a 2;5 translocation; and the third had break points at 14q32 and 2p12. The latter patient showed expression of B-cell antigens and had rearrangements in the immunoglobulin heavy chain and kappa light chain genes. The two patients with the 2;5 translocation were epithelial membrane antigen positive, but did not exhibit rearrangements of immunoglobulin/T-cell receptor genes or expression of T-/B-cell antigens.

UT-MUC-1, a new mucoepidermoid carcinoma cell line, and its radiosensitivity.

Mucoepidermoid carcinoma is a fairly common malignant disease of the salivary glands. It is usually composed of two cell types, mucus-producing mucous cells and cells that have squamous differentiation with or without keratinization. The treatment of choice is considered to be radical surgical removal of the tumor. Radiotherapy has been recommended for high-grade or advanced tumors. Information on the radiosensitivity of mucoepidermoid cancer is scant, but based on clinical experience, the cancer appears to be only moderately radiosensitive. UT-MUC-1 is a newly established cell line from a poorly differentiated mucoepidermoid carcinoma. The cell line is diploid, but with complex karyotype abnormalities, giving a similar DNA index when measured with flow cytometry as that from the original tumor, and produces a tumor with characteristics typical for mucoepidermoid cancer when heterotransplanted to nude mice. The cell line is radiation resistant, with an area under the curve of 2.30 + 0.21 Gy when measured with a 96-well plate clonogenic assay. This correlates with the clinical outcome of the patient and the clinical experience of the radiosensitivity of this tumor type.

Spontaneous remission in acute myeloid leukaemia.

A summary of the literature of adult patients with acute myeloid leukaemia (AML) who have undergone spontaneous remission (SR) is presented together with a report of a patient whose SR was accompanied by cytogenetic remission. There are less than 20 reports of SR since the 1980s. SR is by no means synonymous with cure, since the average duration of the remission is only 7.1 +/- 9.2 months. Neither infections nor transfusions are absolute requirements of SR.

Ring chromosome 20 mosaicism in a girl with complex partial seizures.

The authors report an 11-year-old girl with epilepsy, poor school-performance and minor behavioural disorders. The epilepsy is characterized by complex partial seizures, sometimes progressing secondarily into generalized tonic-clonic seizures, and is poorly controlled by medical treatment. Chromosomal analysis revealed a ring chromosome 20 mosaicism. The affected patient shows signs of ring chromosome 20 syndrome, characterized in the present case by poor school-performance, behavioural disorders and epilepsy.

Transabdominal chorionic villus sampling and amniocentesis for prenatal diagnosis: 5 years' experience at a university centre.

The fetal loss rates and fetal congenital birth defects in 821 transabdominal (TA) chorionic villus sampling (CVS) and 771 amniocentesis (AC) cases were evaluated from a 5-year period (1987-1991) at the University Central Hospital of Turku. The parents were given the option of choosing between the two sampling procedures. CVS was performed, in most cases, at 11 weeks of gestation; and AC, at 15 weeks. The rate of total post-procedure loss was 6.7 per cent in the CVS group and 4.4 per cent in the AC group (p = 0.08). The rate of spontaneous abortions was 1.9 per cent in the CVS group and 1.0 per cent in the AC group (p = 0.10). The number of birth defects was low in both study groups. No limb reduction cases were observed. Mosaicism was noted in 14 CVS cases and in five AC cases. We conclude that TA-CVS is a safe and practical alternative to AC in prenatal fetal karyotyping.

Isolation of two keratinocyte cell lines derived from HPV-positive dysplastic vaginal lesions.

Explant cultures were started from human papillomavirus (HPV)-infected genital lesions in order to isolate and propagate abnormally differentiating cells from squamous intraepithelial neoplasia. A medium with high calcium concentration was used to induce terminal differentiation of cells from surrounding normal epithelium. Two cell lines with extended life-spans were established. The UT-DEC-1 cell line was derived from an HPV-33-positive mild vaginal dysplasia (VAIN I). In cultured UT-DEC-1 cells, HPV 33 DNA was detected with Southern-blot hybridization and the polymerase chain reaction (PCR) technique. The restriction pattern of HPV 33 changed during early passages and flow cytometric analysis detected a decrease in chromosomal DNA content. HPV 33 RNA from the E6-E7 region could be amplified by PCR at late passage. UT-DEC-2 cell line was derived from an HPV-16-positive moderate vaginal dysplasia (VAIN II). HPV 16 DNA was also detected in cultured cells by the PCR technique. The senescence of normal keratinocytes and growth selection in favor of aneuploid cells was observed by flow cytometric analysis at subsequent passages. Karyotype analysis showed clonal chromosomal abnormalities in both cell lines. To date, UT-DEC-1 cells have undergone 40 and UT-DEC-2 cells 25 passages. This study shows that the isolation of HPV-infected dysplastic cells can be achieved by culturing the cells in a medium with high calcium concentration. The cell lines presented provide the opportunity of evaluating the early stages of squamous-cell carcinogenesis.

Characterization and radiosensitivity of UT-EC-2A and UT-EC-2B, two new highly radiosensitive endometrial cancer cell lines derived from a primary and metastatic tumor of the same patient.

UT-EC-2A was established from a patient with moderately differentiated Stage III endometrial adenocarcinoma with squamous metaplasia. UT-EC-2B was established from the same patient 17 months later from a metastasis in the left supraclavicular fossa. The origin of these cell lines was confirmed by DNA identity testing. Nude mice tumors produced by UT-EC-2A and UT-EC-2B cells recapitulated the histology of the original human tumors. Flow cytometric DNA contents of both primary and metastatic human tumors as well as corresponding nude mice tumors were diploid. The S-phase fractions of both cell lines were > or = 30%. The UT-EC-2A cell line was cytogenetically normal. The UT-EC-2B cell line had quite simple karyotype at low passage with an extra i(18p) and a deletion 21q, but at higher passages an additional three-way translocation 5;14;19 was observed. Radiosensitivity of the cell lines was tested with the 96-well plate clonogenic assay. The areas under the survival curves corresponding to the mean inactivation doses of UT-EC-2A and UT-EC-2B were 0.65 +/- 0.10 and 0.60 +/- 0.06 Gy, respectively. Measured survival at 2.0 Gy (SF2) was 0.042 for UT-EC-2A, 0.044 for UT-EC-2B, and 0.2 for skin fibroblasts. These cell lines are among the most radiosensitive human cancer cell lines described in the literature. Studying the characteristics of primary and metastatic cells derived from the same patient provides an opportunity to evaluate tumor progression.

Two novel human B-cell lymphoma lines of lymphatic follicle origin: cytogenetic, molecular genetic and histopathological characterisation.

Two B-cell lines, designated as HF-1 and HF-4, were characterised. The cell lines have complicated karyotype abnormalities including a 14;18 translocation and an 8q24 breakpoint originating from t(2;8)(p11;q24) (HF-1) or t(1;8)(p21;q24) (HF-4). The lines have BCL2 rearrangement and they are positive for CD19, CD20, CD22, CD39. HF-1 is also positive for IgG, and HF-4 is positive for IgM and IgD. On Northern blot analyses, the 2.6-kb and 4.2-kb transcripts corresponding to the major transcripts of CMYC and BCL2, respectively, were seen. In Western blot as well as in FACS (fluorescence-activated cell sorting) analysis the presence of BCL2 protein in the both HF-1 and HF-4 cells was demonstrated. The cell lines are expected to serve as an important tool in the study of the chromosomal mechanism activating cellular oncogenes, the somatic hypermutation mechanism of antigen-activated B cells and the apoptosis of B cells.