A Ki-1 (CD30)-positive human cell line (Karpas 299) established from a high-grade non-Hodgkin's lymphoma, showing a 2;5 translocation and rearrangement of the T-cell receptor beta-chain gene

We describe the characterization of a new human cell line, Karpas 299 (K299), established from blast cells in the peripheral blood of a 25- year-old white man. His illness, which began with enlarged occipital and axillary nodes and weight loss, ended after 7 months with generalized lymphadenopathy, pleural effusion, and bone marrow involvement. A lymph node biopsy showed a large cell lymphoma mainly sinusoidal in distribution. The blast cells with pleomorphic nuclei resembled primitive histiocytes. The cells, which expressed the T-cell- associated markers CD4 and CD5, were positive for HLA-DR, epithelial membrane antigen, and CD30 (Ki-1 antigen). The karyotype was aneuploid and included a translocation 2;5. The site of translocation on chromosome 5 (at 5q35.1) is in the region of the locus of the c-fms oncogene (receptor of the monocyte-macrophage colony-stimulating factor MCSF or CSF-1). The cell line Karpas 299 has the same karyotype and pattern of antigen expression as the patient's cells. Northern blot analysis of RNA showed an active rearrangement of the T-cell receptor beta-chain gene. This is to our knowledge the first Ki-1 antigen- positive line to be established from a case of non-Hodgkin's lymphoma.     

In situ hybridisation analysis of a homogeneously staining region at 11q23–24 in an acute myeloid leukaemia (M5) using yeast artificial chromosomes

An example of a homogeneously staining region (hsr), occurring in an acute myeloid leukaemia (M5) on chromosome 11 in the region of bands q23–q24, has been analysed. In situ hybridisation using yeast artificial chromosome (YAC) DNA demonstrated that the amplification did not include the CD3 gene cluster and did not affect the human trithorax gene known to be disrupted by translocations at 11q23. In contrast, the amplification was shown to include the sequence D11S543 which has been previously mapped to chromosome band 11q24. High resolution analysis using confocal microscopy allowed the individual amplicons to be visualised, and it was shown that the hsr consisted of an 8-fold amplification of the region surrounding the probe D11S543. From previous estimates of human chromosome size it was possible to calculate that the hsr was composed of amplicons approximately 10 megabases in length. It was concluded that the region amplified did not extend as far as the translocation breakpoints occurring at 11q23 in acute leukaemias. © 1993 Wiley-Liss, Inc.     

B-cell non-Hodgkin's lymphoma cell line (Karpas 1106) with complex translocation involving 18q21.3 but lacking BCL2 rearrangement and expression

A B-cell non-Hodgkin's lymphoma (B-NHL) cell line (Karpas 1106) with an unusual three-way translocation involving 18q21.3 has been derived from a patient with mediastinal lymphoblastic B-NHL. Although conventional cytogenetics showed a derivative 18q-identical to that seen in cases with t(14;18)(q32.3;q21.3), no translocations of either chromosome 14 could be detected. Instead fluorescent in situ hybridization analysis using a chromosome-18 paint showed that the segment 18q21.3-18qter had become sandwiched on a derivative chromosome X between segments Xqter-c- Xq28 and 13q12-qter, with the centrometric site of 18q21.3 subband juxtaposed to the X sequences. Pulsed-field DNA blots failed to detect rearrangement of the BCL2 gene. Conventional DNA blots using a variety of restriction digests and both 5' and 3' BCL2 and FVT 1 probes also failed to detect rearrangement in Karpas 1106. A rearranged fragment seen only in HindIII digests with 5' BLC2 probes may represent a local microalteration, which is either a mutation or small deletion involving the HindIII site as seen in other cases of B-NHL. Neither BCL2 RNA nor BCL2 protein expression were detected. These and other data suggest that genes at 18q21.3, other than BCL2 and FVT1, may be targets for translocation in certain subgroups of B-NHL.     

Somatotype and disease prevalence in adults

We examined the association between the somatotype and its main components (endomorphy, mesomorphy and ectomorphy), and the prevalence of several chronic diseases. The data were obtained from a cross-sectional survey designed to assess somatotype and morbidity with special reference to most often diagnosed diseases. The study population comprised 524 men and 250 women. The subjects underwent laboratory tests and clinical and anthropometric examinations. Of all examined workers, 94.8% fell into the five somatotype categories; of these, 394 were endomorphic mesomorphs. The most common somatotype was endomorphic mesomorph for men and mesomorph-endomorph for women. In five disease groups, prevalence was significantly related to a somatotype. Mesomorphic endomorphs most frequently suffered from digestive system diseases (40.6%, p < 0.05), neuroses (30.1%, p < 0.05), and radiculitis lumbosacralis (15.4%). The prevalence of arterial hypertension in mesomorph-endomorphs (37.1%), endomorphic mesomorphs (35.5%), and mesomorphic endomorphs (34.3%) was equal. In both genders, those with the highest endomorphy and mesomorphy and the lowest ectomorphy, grouped by cluster analysis, were those who suffered most frequently from arterial hypertension and liver disease. The authors conclude that the somatotype having a dominant mesomorphy and marked endomorphy constitutes a risk factor as a particular predisposition toward certain diseases and requires body weight control.     

Noninvolvement of chromosome 16 in karyotype evolution of acute myeloid leukemia in a patient with a heritable fragile site on 16q22

A fragile site on the long arm of chromosome #16 (q22) was detected in a 24-year-old man with pancytopenia. During the course of the disease he developed an inverted duplication of region q11-12 of chromosome #1 and a translocation between chromosomes #9 and #13: t(9;13)(p22;q32). These abnormalities, as well as an additional iso-like marker chromosome that consisted of one normal 9p and the abnormal 9p arm, were detected in Epstein-Barr nuclear antigen-positive B-cell cultures. Two years later, evolution of the abnormal clone with loss of chromosome #7 and, subsequently, chromosome #22 occurred in connection with development of acute myeloid leukemia. Although the heritable fragile site on chromosome #16 was present in all cell populations investigated, it was not involved in the evolution of the abnormal karyotype. This fragile chromosome #16 also was found in 4 of 11 family members in whom chromosome analysis was performed, thus suggesting this aberration was inherited in a dominant autosomal pattern. The incidence of the heritable fragile site in normal and leukemic cells of the patient, as well as stimulated blood cultures of his relatives, are reported. In addition, the possible relationship between this constitutional chromosome breakage syndrome and the occurrence of leukemia is analyzed.     

Investigations on karyotype evolution in patients with chronic myeloid leukemia (CML)

Summary In an attempt to relate karyotype evolution to clinical and hematological data serial chromosomal analyses were performed in 31 patients with chronic myeloid leukemia (CML), both in chronic and acute phases. Our results in Philadelphia chromosome (Ph¹)-positive CML are in line with karyotype profiles described in the literature. In addition, we report on chromosomal findings in 4 cases of Ph¹-negative disease, one presenting with an iso17q chromosome in the acute phase, an aberration otherwise typical for acute transformation in Ph¹-positive CML. The same chromosomal abnormality was observed in a small population of Ph¹-negative cells present in one of two patients with mixed Ph¹-positive/Ph¹-negative CML. The first case of a female patient with the loss of a sex chromosome in Ph¹-positive cells is reported. Two patients with unusually long and mild chronic phases despite the presence of trisomy 8 in their karyotypes are described. Our findings suggest that the order of appearance of additional chromosomal changes of CML is of prognostic significance for the progression and the clinical picture of the disease.     

Molecular analysis of chromosome 20q deletions associated with myeloproliferative disorders and myelodysplastic syndromes

Acquired deletions of the long arm of chromosome 20 are found in several hematologic conditions and particularly in the myeloproliferative disorders and myelodysplastic syndromes. The spectrum of diseases associated with 20q deletions suggests that such deletions may mark the site of a tumor suppressor gene that contributes to the regulation of normal multipotent hematopoietic progenitors. We present here the first detailed molecular analysis of 20q deletions associated with myeloid disorders. Thirty-four microsatellite primer pairs corresponding to loci on 20q have been used to study DNA samples from two cell lines and from highly purified peripheral blood granulocytes obtained from seven patients. In addition, Southern analysis of cell line DNA has been performed using 19 DNA probes that map to 20q. Three conclusions can be drawn from our results. Firstly, molecular heterogeneity of both centromeric and telomeric breakpoints was demonstrated, thus supporting the existence of a tumor suppressor gene on 20q. In addition many of the breakpoints have been mapped to small genetic intervals. Secondly, our results define a commonly deleted region of 16-21 cM which contains ADA, PLC1, TOP1, SEMG1, and PPGB. Several candidate tumor suppressor genes lie outside the common deleted region including SRC, HCK, p107, PTPN1, and CEBP beta. Thirdly, the data allow integration of genetic and physical maps and have refined the map positions of multiple genes. These results will facilitate attempts to identify candidate hematopoietic tumor suppressor genes on 20q.