Search

Six patients with chronic myelogenous leukemia and a complex Philadelphia (Ph1) translocation are described. The complex Ph1 translocations were a three-way translocation in five patients and a five-way translocation in one. Additional chromosomal aberrations were detected in four of five patients when the blastic crisis supervened. The median survival time was 42 months. The remaining patient died of acute myocardial infarction 23.5 months after the diagnosis of CML was made. There seems no difference between these six patients and those with the standard Ph1 with respect to clinical, hematologic and cytogenetic findings.

We report a boy with some clinical symptoms compatible with a diagnosis of incomplete DiGeorge syndrome. He had a dismorphic face, micrognathia, cleft palate, and heart anomalies similar to DiGeorge syndrome, but lacked aplasia of the thymus or hypoparathyroidism typical of the syndrome. High-resolution banding analysis revealed that his karyotype was 45,XY,-14,-22, +der(14)(14pter----14q32.32::22q11.21----22qter), the consequence of a maternal reciprocal translocation between chromosomes 14 and 22. Precise localization of the gene responsible for the present DiGeorge syndrome was assigned to subband 22q11.1.

Nonspecific cross-reacting antigen (NCA) is a member of the carcinoembryonic antigen (CEA) gene family. Recently, a DNA segment for part of the human NCA gene was isolated and sequenced. We mapped this gene by Southern blot analysis of hybrid cells and by in situ hybridization. The Southern blot analysis indicated that the NCA gene is on human chromosome 19 and the in situ hybridizations localized the gene to band 19q13.2.

A combination of cefmenoxime (CMX) and cefsulodin (CFS) which has a broad spectrum on various bacteria including Pseudomonas aeruginosa was evaluated for severe infections associated with hematological malignancies. Seventy one patients were treated with the combination therapy. Among them, 57 patients were evaluable for the effectiveness. Fourteen patients were not evaluable because 10 patients were subjected to additional therapy such as gamma-globulin, interferon, radiation and pulse therapy of a large dose of methylprednisolone, 3 were prophylactically treated and the remaining one was a patient with disseminated bone marrow metastasis of prostatic cancer and not a patient with a hematologic malignancy. Excellent responses were obtained in 24 (42.1%) patients and good response in 12 (21.1%) patients, with a total rate of effectiveness of 63.2%. Three patients who were treated prophylactically and one patient who suffered from prostatic cancer with metastasis to bone marrow, were included in the final evaluation of side effects. Side effects were observed in only one patient (1/61, 1.6%). Mild neutropenia was identified in a patient of 78 years of age in 4 days after the combined regimen was started. Neutropenia disappeared soon after the cessation of the treatment. These results showed that a combination of CMX and CFS was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.

We established the subline RT-BMV-C6 from the parent human neuroblastoma cell line RT-BM by a process that required repeated subculture of cells, which were prone to disaggregation. RT-BMV-C6 and the parent cloned line, RT-BM-1, had an identical marker chromosome, confirming that both lines were derived from a common progenitor. In the analysis of surface antigen expression, RT-BMV-C6 did not react with UJ-127-11, Leu7 or KP-NAC2 MAbs to which RT-BM-1 showed positive binding. The levels of both N-myc amplification and expression in RT-BMV-C6 were twice as high as the level obtained in RT-BM-1. Colony-forming efficiency in soft agar was 2.0 +/- 0.8% for RT-BMV-C6 and 3 times greater than that for RT-BM-1 (0.6 +/- 0.1%). When 100 x 10(6) cells of RT-BM-1 and RT-BMV-C6 were inoculated into nude mice, tumor incidence was significantly higher for RT-BMV-C6 (6/6; 100%) than for RT-BM-1 (0/6; 0%). Our data show that N-myc is closely related to tumorigenicity in NB. When RT-BM-1 and RT-BMV-C6 were co-cultured with a new synthetic retinoid, polyprenoic acid (E5166), and dibutyryl cyclic AMP, RT-BM-1 was induced to neuronal differentiation, defined by the formation of neuronal processes and expression of neurofilaments, whereas RT-BMV-C6 was not. However, when exposed to E5166, N-myc expression of RT-BMV-C6 was more strongly reduced than that of RT-BM-1, and colony formation of RT-BMV-C6 was significantly inhibited as compared to RT-BM-1. These findings suggest that the reduction of N-myc expression might closely correlate with growth inhibition accompanying neuronal differentiation of neuroblastoma cells.

We observed double minute chromosomes (dmin) and a homogeneously staining region (HSR) in the same metaphase cells obtained from a retinoblastoma cell line, Y79. All of the 132 metaphases examined contained an HSR on the short arm of chromosome 1(1pHSR) and five cells (3.8%) had two to four dmin. To determine whether 1pHSR and dmin carried amplified N-myc sequences, we performed an in situ hybridization using an N-myc probe. Silver grains clustered on and along the 1pHSR, but not on the dmin. These findings indicate that the HSR on chromosome 1 is associated with amplification of N-myc in Y79 cells.

Rearrangement of the breakpoint cluster region (bcr) and the chromosomal location of c-abl and 3'-bcr were studied in two patients with Philadelphia chromosome (Ph1)-negative chronic myelocytic leukemia (CML). One patient (patient 1) had a normal karyotype and the other (patient 2), 46,XY,inv(3)(q21q26). Both patients showed the bcr rearrangement by Southern blot analysis with a 1.2kb 3'-bcr probe. In situ hybridization studies demonstrated the location of the homologous sequences of bcr on chromosome 22 in patient 1, and on chromosomes 9 and 22 in patient 2. These findings indicate that the morphologically normal-looking chromosomes 9 and 22 in patient 2 are the result of a retranslocation between chromosomes 9q+ and 22q-, abnormalities which were first formed by a standard Ph1 translocation.