Donor origin of Graves disease in a BMT recipient: evidence from FISH studies of thyroid tissue.
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Biomedical subjects
Publications and source records attributed to J R Kowalczyk.
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Dexrazoxane (DEX) prevents the formation of free radical, lipid peroxidation and cardiotoxicity caused by anthracyclines. Due to a concern about its possible interference with anthracyclin cytotoxicity, the in vitro effect of DEX on daunorubicin (DNR) cytotoxicity, cell cycle and induction of apoptosis by annexin-V was investigated. The sensitivity to DEX, DNR and their combination was tested by the MTT assay in human promyelocytic leukemia HL-60, the erythroid blast crisis CML K562 cell lines and in 45 children with ALL and AML. Cell cycle analysis and annexin-V expression were performed by flow cytometry. It has been observed that DEX itself weakly, but significantly caused cytotoxicity in both cell lines and in patient samples, especially in initial ALL samples. DEX sensitized K562 and HL60, but not patient samples, to cytotoxicity of DNR. The percentage of necrotic/apoptotic cells, as detected in cell cycle analysis and annexin V staining, was higher after exposure to DEX +/- DNR, when compared to respective samples not treated with DEX, in both cell lines but not in patient samples. Expression of annexin V induced by DEX in both cell lines was enlarged, regardless of the presence of DNR. This difference was not observed in patient samples, however, the number of cells expressing annexin V was higher after exposure to DEX +/- DNR in comparison to respective samples not treated with DEX. In conclusion, it seems that DEX possibly has no impact on the sensitivity of childhood leukemic blasts to DNR, however, has weak cytotoxic properties itself.
A case of ALL in a 2 1/2-year-old boy with fatal outcome is presented. Cytogenetic analysis revealed a hypodiploid karyotype: 45,X-Y,-2,+der (2)t(Y;2),-12,i(17q),+mar. Some metaphases represented a sideline with 44 chromosomes and monosomy 8 was a consistent anomaly. These findings are rather uncommon in ALL. Hypodiploidy and the translocation, however, indicated poor prognosis in this case.
Fourteen patients diagnosed as having multiple myeloma were studied cytogenetically. In eight patients a sufficient number of metaphases was obtained and four of them showed abnormal karyotypes of bone marrow cells. Hypodiploidy was a consistent finding, as was the involvement of chromosome 9.
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Using dicentric chromosomes and acentric fragments as indicators of radiation sensitivity, a study has been performed on human lymphocyte chromosomes by irradiating peripheral blood cells at G0. Donor-to-donor variation has been noticed regarding radiation sensitivity even when metaphase spreads were scored at the first cell cycle. Thus, it appears that, at the present state, use of chromosomal damage in peripheral blood cell cultures as an effective biological dosimeter for effects of radiation is questionable.
Three children with acute leukemia and t(4;11)(q21;q23) are presented. Two of the cases showed very unusual karyotypic findings and long survival for the type of leukemia. In case B.T., the original karyotype change observed was t(4;11), with other changes (+4q-,+11q+,+6,+10) appearing during the last stages of the disease. In case R.B., the translocation was accompanied by many numerical and morphological chromosome changes, with a near-tetraploid chromosome number. In both of the above cases, remission was associated with a normal marrow karyotype. In case D.C., only the t(4;11) was observed. The number of cases with t(4;11) and acute leukemia published so far is 36, including the three cases presented by us. As this disease is usually characterized by a relatively short survival, the possible reasons for the remarkably long survival in two of our patients are discussed in relation to the rather unusual cytogenetic findings.
Complete remission rates, remission duration, and survival were established in children with acute lymphoblastic leukemia (ALL) with chromosome #1 anomalies, and the results were compared with those in patients with normal karyotypes or other chromosomal changes. Even though the complete remission rate did not differ significantly among the three groups, remission duration and survival were significantly longer in children ALL and chromosome #1 anomalies as compared with those in the other two groups.
Chromosome studies were performed on the bone marrow cells of 42 children with newly diagnosed acute lymphoblastic leukemia (ALL). All the children were subsequently treated with the same protocol. Chromosomal abnormalities were found in 25 patients, i.e., in 59.5% of the cases. Hyperdiploidy was observed in 21.4% hypodiploidy in 14.3%, and pseudodiploidy in 23.8% of the children. The most frequent structural aberrations were translocations, which were found in half of the patients with abnormal karyotypes. Chromosomes #5, #6, #7, #9, #14, #17, and #21 were involved in different types of changes most frequently. Because these findings correspond with observations published by others, they can be regarded as evidence of nonrandom involvement of these chromosomes in rearrangements in ALL. Special attention should be also paid to the deletion of 6q, which seems to be relatively common in ALL. In 12 cases, clonal evolution of karyotypic changes was observed.
A case of probable secondary lymphoma, poorly differentiated lymphocytic lymphoma (PDLL), is described in which two chromosomal translocations were observed, i.e., t(10;19)(q11;q13) and t(1;6)(q21;p11.1-2). A consistent numerical aberration was monosomy of chromosome #21. Accumulation of more data on secondary lymphomas is necessary in order to reach a general conclusion as to whether or not there are any nonrandom chromosomal aberrations that differentiate primary from secondary lymphomas.
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Complicating (secondary) leukemias in 20 patients, 18 of whom had various forms of neoplasia treated with chemotherapy and/or radiation, have been examined in regard to the karyotypic findings present in the leukemic cells of the marrow. In addition, the published cases of complicating leukemia have been tabulated. Based on the results of the present study and those in the literature it appears that chromosomes #3 and #17 should be stressed as being nonrandomly involved in complicating leukemia in addition to the previously stressed chromosomes #5 and #7. The results of the present study are discussed in relation to those reported in the literature, and stress put on the significance of cytogenetic changes in relation to possible causative factors of the complicating leukemia. The hypothesis is advanced that these nonrandom chromosome changes may reflect causative specificity of the complicating leukemia and that a concerted effort must be made to obtain more cogent information on the role of noxious agents in the causation of complicating leukemia.
Different types of chromosomal damage in the G(o) phase of human lymphocytes have been studied in the first (M1) and second cell lymphocytes (M2). Large populations of cells containing one dicentric chromosome and one acentric (DIC+) were observed in the second cycle. This indicates that these dicentric and acentric fragments have a normal distribution in M2 or, arose through loss of one acentric fragment (AC) from cells containing one dicentric and two acentric fragments (DIC++) in M1. Similarly, a large number of metaphases in M2 have unpaired differentiated ACs. Our data indicates that aberrant metaphases containing single AC or a DIC+ may undergo normal cell division and that these cells may not represent cells in the first cycle only, as was suggested by earlier workers. For radiation experiments to G(o), a desirable time to harvest human lymphocyte cultures appears to be 72 hours and screening of M1 and M2 cells by sister chromatid differentiation.