Biomedical subjects
Publications and source records attributed to G Barbata.
It is demonstrated by DNA electrophoresis analysis, morphological observations and TdT in situ reaction, that Paracentrotus embryos if treated with TPA plus heat undergo an apoptotic reaction. Indication is also obtained that non treated embryos undergo spontaneous apoptosis at the early pluteus stage, especially in the districts of arms and intestine. The possible meaning of this latter observation is discussed.
A variant cell population, isolated from V79-C13 Chinese hamster cells after two consecutive treatments with methyl methanesulphonate (MMS), was found to be highly resistant to killing by this alkylating agent. The resistant cell line was cytogenetically characterized both by the presence of a stable translocation involving metacentric chromosome 2 and acrocentric chromosome 6 and by a supernumerary chromosome originated by the duplication of a small telocentric chromosome. This cell population also showed a transient transformed phenotype, seen as formation of transformed foci containing cells with high chromosomes counts and multiple chromosomal aberrations. As MMS-resistance and karyotype changes are permanent and heritable traits, we suppose that they are related events.
We report the results of a molecular investigation of 11 patients affected by Waldenström's macroglobulinemia, a rare B-cell malignancy characterized by an excessive proliferation of immunoglobulin (Ig)M-secreting plasmacytoid cells. In particular, we studied the interleukin-4 (IL4) gene, which codes for a B-specific growth factor capable of stimulating the proliferation and differentiation of secreting plasma cells. By Southern hybridization, in three patients we found the presence of additional bands in comparison with the expected pattern; moreover, these bands showed a different degree of intensity.
Results on sister chromatid exchange (SCE) frequency and interchromosomal distribution in bone marrow and peripheral blood cultures from patients with Waldenström's macroglobulinemia are reported. PHA-stimulated bone marrow cultures showed increased SCE frequencies in all 12 patients examined. The increase was particularly high in two cases (17.07 and 16.77 SCE/cell, respectively) and, in one of them, a very high SCE level was found in PHA-stimulated peripheral blood culture (40.81 SCE/cell). In LPS-stimulated cultures, increased SCE levels were observed in some patients. Comparison between SCE frequency in bone marrow cell cultures with either mitogen showed a significant increase in PHA-stimulated cultures. Analysis of the interchromosomal SCE distribution revealed significant differences with respect to the control values; however, these differences were variable in the different patients. In pooled data of PHA-stimulated bone marrow cultures, there were differences between expected and observed SCEs in chromosomes 1 and 2 and in B, E, F, and G chromosome groups. Results of cell cycle modifications are also reported.
We report the results of cytogenetic studies of direct bone marrow (BM) preparations and of short-term BM and peripheral blood (PB) cultures from 17 patients with Waldenström's macroglobulinemia. We noted clonal chromosome changes in 10 patients. Abnormalities affected chromosomes X, Y, 2, 4, 5, 15, 16, 18, 19, 20, 21, and 22; in particular, chromosomes 2, 4, and 5 were involved in structural changes: a homogeneously staining region [hsr(2)], a der(4)t(4;?)(q32;?), and a 5q+. The other chromosomes were involved in numerical abnormalities, such as pseudodiploidy (a 46,X, -X, + 15 clone), loss of chromosome Y, and monosomy of chromosomes 16, 18, 19, 20, 21, and 22. Nonclonal chromosome rearrangements were also observed. The results are discussed in comparison with the few data reported in the literature, and the finding of an hsr in the long arm of chromosome 2 is emphasized; indeed, this is the first report of hsr in WM.
We have report the results of cytogenetic studies carried out in eight patients with acute nonlymphocytic leukemia developed after primary neoplasias. In seven of the reported cases, clonal chromosome aberrations were found, some being specific of de novo acute nonlymphocytic leukemia (ANLL). Numerical abnormalities were detected, such as the total monosomy of chromosomes 5, 7, 21, trisomy of chromosomes 8, 11, 15, and duplication of chromosome Y. Structural changes were also observed: a del(12)(p12), a del(16)(q22), the translocations t(3;5)(p21;q35),t(3;7)(p21;q35), and t(12;14)(p12;q32) and other changes involving chromosome 8. The finding of a hypertetraploid karyotype with complex structural chromosome aberrations in a patient with erythroleukemia, developed after non-Hodgkin's lymphoma, is of particular interest. Data reported in this work are discussed with regard to the relationship between secondary and de novo ANLL and the finding of chromosome aberrations other than total or partial monosomy of chromosomes 5 and 7 is emphasized.
We utilized, in CHO cells, the cytoplasm preservation technique to evaluate the micronucleus frequency at different busulphan concentrations, and the indirect immunofluorescence technique, using sera obtained from patients with scleroderma (CREST variant), to analyze if busulphan-induced micronuclei have kinetochores. Results show that this alkylating agent is capable of causing a significant increase of micronuclei in vitro, a great part (40%) of them having CREST-positive kinetochores. These findings confirm the clastogenic effect of busulphan and reveal a considerable capability of this agent to induce aneuploidy. These results are examined taking into account the high incidence of secondary neoplasias induced by chemotherapy with alkylating agents utilized against primary neoplasias.
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Simultaneous involvement of bands 8p11 and 16p13 in a primary, even though rare, chromosomal translocation recently described in acute nonlymphocytic leukemia may be of crucial interest in some subtypes of this acute leukemia, particularly in the monocytic form. In the present report we describe this translocation in acute nonlymphoblastic leukemia FAB M4, possibly secondary to Hodgkin's disease, though it is also possible that the leukemia may have developed de novo. The aberration t(8;16)(p11;p13) was present in 100% of direct and cultured bone marrow cell preparations. A very high frequency of cells with nonclonal structural chromosome aberrations was also observed in peripheral blood cultures (more than 53%). Random translocations and deletions constituted most of the observed alterations. These findings are discussed with regard to the relationships between secondary leukemias and intensive polychemotherapeutic treatments of primary neoplasias.
A rare cytogenetic finding in chronic myeloid leukemia is reported. It consisted in a "masked" Philadelphia chromosome, resulting from an unusual translocation between chromosomes #22 and X. The t(X;22) was present in 100% of direct and cultured bone marrow cell preparations. Chromosome #9 did not seem to be involved in the formation of the Ph marker. Involvement of the X chromosome in karyotypic changes of hematologic diseases, with particular respect to chronic myeloid leukemia, is discussed.
Clonal chromosome changes were found in a patient with FAB-L1 acute lymphoblastic leukemia. The changes consisted of a t(8;14)(q24;q32), Burkitt type, and a rare marker chromosome 1p-. The breakpoint in this chromosome was localized at band 1p22. Both these abnormalities were present in 100% of unstimulated peripheral blood cells. The detection of the t(8;14) in a case of acute lymphoblastic leukemia, without a clear evidence of B immunophenotype and with an unusual long survival (more than 3 years), is discussed.
Several karyotype changes observed during the blastic phase in 2 patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) are reported. Rearrangements involving chromosome 1, i.e., translocations, a pericentric inversion and trisomies of its long arm, are described. In the first patient whose chronic phase was very long (17 years), the uncommon association between i(17q) and Ph duplication has been observed during the blastic phase, beside the involvement of chromosome 1. In the second patient, additional abnormalities involving chromosomes 1, 2, 4, 8, 18 and 21 were present. Of particular interest is the finding of a t(1;2). In this case, the presence of hyperdiploid cells with 49-50 chromosomes, prevailing at the blastic crisis, was due to the evolution of the hypodiploid clone with the 45,XX,t(9;22),-21 karyotype found during the chronic phase. The occurrence of chromosomal changes involving chromosome 1 during the blastic phase of CML is emphasized.
We report a complex rearrangement observed in both the short and long arms of chromosome #3 in a patient with Ph-positive chronic myeloid leukemia in blastic crisis and without thrombopoietic abnormalities. The rearrangement consisted of a complex translocation, t(3;9;22)(p21;q34;q11), and a paracentric inversion of the long arm of the same chromosome #3 involved in the translocation. Involvement of chromosome #3 in complex translocations in chronic myeloid leukemia and the relationship between 3q anomalies and thrombopoietic diseases are discussed.
Cytogenetic findings obtained during the clinical course in two patients (one child and one adult) with Ph-positive acute lymphoblastic leukemia (ALL) are reported. Chromosomal abnormalities in addition to Ph chromosome were detected in both patients. At the beginning of the disease, such abnormalities consisted of the trisomy of chromosome 1 and monosomy of chromosomes 8 and 9, with a sub-line 45, XY, Ph, -8 in the child; in the adult patient a hyperdiploid clone with 57-59 chromosomes and Ph duplication was present. At relapse, the same karyotypic anomalies reappeared in the child, whereas in the adult a high frequency of chromosomal rearrangements, such as ring and dicentric chromosomes, was observed after cranial irradiation. The occurrence of chromosomal abnormalities additional to Ph during the clinical course in ALL patients is discussed, taking into account data from the literature concerning the lymphoid blastic crisis in chronic myeloid leukemia patients.
Chromosome studies of five patients with myelofibrosis and myeloid metaplasia were carried out on bone marrow cells and/or on peripheral blood without PHA. Abnormal clones were found in three patients. Such clones were a minority, compared with the number of cells with normal karyotypes in all three patients. Chromosomes abnormalities consisted of 5q- (case 5), 13q- (case 2), and a small supernumerary acrocentric marker (case 3). One of our five patients, a woman aged 75 (case 1), showed a constitutional karyotype 46,XX,inv(5)( p15q11 ). The same chromosome rearrangement was present in 100% of the stimulated peripheral lymphocytes of this patient and in one of her sons with a normal phenotype. One patient (case 4) had a normal karyotype. These results are discussed and compared with data from the literature concerning myelofibrosis and other myeloproliferative diseases.
Cytogenetic studies in peripheral blood and bone marrow cells from a female patient (aged 31 years) with inherited aplastic anemia and without other congenital anomalies are reported. Endoreduplication was increased in stimulated peripheral lymphocytes in several investigations. Chromosome breaks were shown to be near the control frequency, although chromatid exchange figures and dicentrics were present. Cytogenetic analysis was extended to the three children of our patient. Abnormal clones were detected in bone marrow preparations of our patient in all cytogenetic investigations. At the first examination, two of these clones were prevalent, with their karyotypes being 48,XX, +9, +16 and 46,XX,dup(1)(q24----q32),t(17;?)(p12-13;?). The prevailing karyotype after 2 years was 46,XX,t(17;?)(p12-13;?). Involvement of chromosomes #1 and #17 is discussed, taking into account data from the literature concerning several human neoplasias.
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