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Biomedical subjects

G Saglio

Publications and source records attributed to G Saglio.

At least 199 records · Page 11Linked to original sources
PubMed1988

Selective growth response to IL-3 of a human leukaemic cell line with megakaryoblastic features.

A new human leukaemic cell line (M-O7) with the phenotypic characteristics of CFU-mega is described. Its cells are positive for T200 leucocyte common antigen (LCA) and negative with MAbs recognizing T and B cells and mature myelomonocytic antigens. In contrast, they react with MAbs recognizing antigenic determinants common to multi-lineage (CD13, CD33, CD34) and to bipotent erythromegakaryoblastic (CD36, H25) haemopoietic precursors, and with MAbs specific for platelet glycoproteins (CD41w, CD42w). A small proportion (10%) of the cells were large and multinucleated, and on electron-microscopy examination showed peripheral splitting of platelet-like cytoplasm particles. When transferred to a serum-free Iscove modified Dulbecco's medium supplemented with human insulin and transferrin, M-O7 cells stop proliferating. Of the haemopoietic growth factors tested for their ability to restore the proliferative activity of this quiescent population, only rH IL-3 proved effective. Moreover, it also increased the cloning efficiency in methylcellulose more than any other CSFs. The M-O7 cell line may provide a valuable tool for the biological assay of IL-3, and a model for biochemical studies of the megakaryocytic lineage.

Cell Line↗
PubMed1988

Meiotic recombination in the beta globin gene cluster causing an error in prenatal diagnosis of beta thalassaemia.

In the course of a prenatal diagnosis for beta thalassaemia by linkage analysis of restriction fragment length polymorphisms, a homozygous beta thalassaemia fetus was misdiagnosed as beta thalassaemia trait. Extensive studies of the polymorphic sites within the beta globin gene cluster in all the members of the family resulted in the conclusion that the paternal chromosome 11 of the newborn was different from that expected. Paternity was confirmed by HLA typing and blood group studies. The analysis of another polymorphic locus on chromosome 11 within the family was in agreement with the possibility of a crossing over between the two paternal chromosomes in a region 5' to the beta gene, previously indicated to contain a 'hot spot' area for recombination. This report underlines the risk of performing prenatal diagnosis using restriction polymorphisms 5' to the beta gene.

Diagnostic Errors↗
PubMed1988

Variability of the molecular defects corresponding to the presence of a Philadelphia chromosome in human hematologic malignancies.

By analyzing a total of 107 patients affected by chronic myelogenous leukemia (CML; chronic and blast crisis) or lymphoid and myeloid Philadelphia chromosome (Ph') positive acute leukemias, we have investigated the relationship between the molecular defect on the Ph' chromosome and the associated hematologic phenotype. As expected, approximately half of the Ph' positive acute leukemias showed a breakpoint on chromosome 22 falling outside the "breakpoint cluster region" (bcr) known to be involved in CML. Surprisingly, seven of 80 CML cases in chronic phase also showed rearrangements falling outside the bcr region. In two of these cases the breakpoint on chromosome 22 was mapped between 9 and 12 kb upstream to the bcr region. In another case, the breakpoint was located approximately 16 kb downstream to bcr. In the remaining four cases, the precise position of the rearrangement could not be localized with the available bcr probes. DNAs from patients with CML blast crises showed classical bcr rearrangements. No molecular changes were observed during the progression of the disease in six patients whose DNA from both a chronic and acute phase was available. Our results seem to indicate a greater degree of variability of chromosome 22 breakpoints in CML than previously observed, and the lack of additional rearrangements on the Ph' chromosome in CML blast crises with respect to chronic phase.

Adult↗
PubMed1988

Delineation of specific beta-thalassemia mutations in high-risk areas of Italy: a prerequisite for prenatal diagnosis.

In this study, we defined by haplotype characterization combined with oligonucleotide hybridization or direct restriction endonuclease analysis the specific beta-thalassemia mutations in a representative sample of beta-thalassemia chromosomes from patients with homozygous beta-thalassemia originating from different parts of Italy. We characterized the mutations in 90% of the thalassemia chromosomes and found that three mutations, namely the beta(+)IVS 1-110, beta (0)-39 and beta(+)IVS 1-6 are prevalent in the Italian population. Most of the patients investigated were compound heterozygotes for two beta-thalassemia mutations, and only a few were homozygotes for one mutant. On the basis of these findings, we predict that prenatal diagnosis in this population would be feasible in most cases by fetal DNA analysis with the oligonucleotide method using a limited number of oligonucleotide probes selected after screening parents for the most common beta-thalassemia mutations. We have also devised a method based on hybridization with a mixture of two oligonucleotides that allows rapid and simultaneous screening of prospective parents for the two most frequent mutations in Italians, the beta(+)IVS 1-110 and beta(0)-39 mutants. This method may be applicable to prenatal diagnosis in cases at risk for the genetic compound of these mutations.

DNA Mutational Analysis↗
PubMed1987

Duplication of Ph and of 9q+ chromosomes during the blastic transformation of a CML case.

We describe the blastic transformation of a case of chronic myelocytic leukemia in which, among other abnormalities, one extra Philadelphia and one extra 9q+ were observed. Molecular studies and analysis of the clonal evolution of the karyotype led to the interpretation of such an unusual finding as the result of nondisjunction, rather than of a double t(9;22) translocation.

Adult↗
PubMed1987

A benign form of thalassaemia intermedia may be determined by the interaction of triplicated alpha locus and heterozygous beta-thalassaemia.

In this paper we report that the combination of a triplicated alpha globin locus with heterozygous beta-thalassaemia produces a clinical phenotype of thalassaemia intermedia in five Italian subjects from four unrelated families, while in two other cases the phenotype was thalassaemia minor. The haematological findings of the five patients were uniform, producing a benign form of thalassaemia intermedia, transfusion independent, with a long life expectancy. The pattern of inheritance of the two genetic determinants and the more pronounced beta/alpha globin chain imbalance, demonstrates that the genetic combination is indeed the cause of the phenotype. The pattern of restriction enzyme site polymorphisms suggests the presence of the beta IVS I 110 G----A mutation at least in three of these cases.

Adolescent↗
PubMed1987

Germ-line configuration of the T-cell receptor beta-chain gene in B-cell chronic lymphoproliferative disorders which co-express T-cell antigens.

In 7 cases of chronic B-cell lymphoproliferative disorders-6 chronic lymphocytic leukaemias and 1 non-Hodgkin lymphoma in leukaemic phase--which co-expressed T-cell markers (CD3, CD2) the clonal origin was investigated at the DNA level. In accordance with the diagnosis, all cases showed a monoclonally rearranged configuration of the immunoglobulin genes. On the contrary, the T-cell receptor beta chain gene always retained a germ-line organization. These findings demonstrate that B-cell chronic lymphoproliferative disorders which co-express T-cell-related markers are truly composed of monoclonal B-cell elements.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

The 3' ends of the deletions of Spanish delta beta zero-thalassemia and black HPFH 1 and 2 lie within 17 kilobases.

Spanish delta beta zero-thalassemia, a mild thalassemic condition characterized by increased level of hemoglobin (Hb) F production during adult life, is known to be due to a large deletion starting within the beta globin gene cluster and extending beyond the 3' breakpoint of any other similar deletional defects so far identified. By molecular cloning and by genomic mapping we now demonstrate that the deletion of Spanish delta beta zero-thalassemia ends at approximately 11 and 17 kilobases (kb) downstream to the 3' endpoints of black hereditary persistence of fetal hemoglobin (HPFH) type 1 and 2, respectively. As suggested by the complete characterization of this and other deletional defects involving the beta globin gene cluster, the 5' and 3' breakpoints of several deletions cluster in rather restricted DNA areas, further strengthening the idea that common molecular mechanisms may operate in causing these deletions.

Base Sequence↗
PubMed1987

Rearrangement of the c-myc oncogene with heavy-chain immunoglobulin enhancer in tumor DNA from an acute lymphoblastic leukemia patient.

The DNA obtained from the leukemia cells of an acute lymphoblastic leukemia (ALL, L3 type) with a pre-B-phenotype and a typical t(8;14) chromosomal translocation showed a rearrangement juxtaposing the c-myc gene and the immunoglobulin (Ig) heavy-chain gene enhancer. This abnormality was only present in the leukemia cells of the patient and correlated with the clinical course of the disease. The breakpoint on chromosome 8 occurred within c-myc intron 1, between 790 and 638 base pairs upstream of c-myc exon 2. This breakpoint position was the nearest to the c-myc exon 2 so far described in Burkitt's type lymphoma-leukemias, and it mapped very near to the location of a major cryptic promoter used by truncated c-myc genes. In spite of what was detected in a human lymphoma cell line (Manca) carrying a similar rearrangement, in this case the amount of c-myc transcript was not increased compared to an Epstein-Barr virus-transformed normal lymphoblastoid cell line obtained from the same patient. This may in part be due to the breakpoint position and to the fact that the efficiency of the major cryptic promoter present within the first intron could have been affected by the translocation event. Finally, as previously suggested by others, the phenotype expressed by the leukemia cells supported the notion that this particular type of rearrangement (linking together the c-myc gene and the Ig heavy-chain gene enhancer element) may be associated with a subgroup of B-ALLs showing an immunologic phenotype relatively more immature than that of classical B-ALL.

Adult↗
PubMed1987

Sardinian delta beta zero-thalassemia: a further example of a C to T substitution at position -196 of the A gamma globin gene promoter.

Selective overexpression (50- to 100-fold) in adult erythroid cells of either G gamma or A gamma fetal globin gene is observed in hereditary conditions known as delta beta zero-thalassemia and hereditary persistence of fetal hemoglobin (HPFH). Recently, a C----T change at position -196 of an overexpressed A gamma globin gene from an Italian HPFH was hypothesized, on the basis of indirect evidence, to represent the cause of the functional defect. We now show that the same mutation is present in a different overexpressed A gamma-globin gene from a Sardinian patient with a different syndrome (delta beta zero-thalassemia). The Sardinian A gamma globin gene differs from both the HPFH and the normal A gamma globin gene at nucleotide 1,560 in the noncoding portion of the third exon, where an A is deleted. In addition, the mutant -196 A gamma-globin gene is linked to a normal beta globin gene in HPFH, and to a beta-thalassemic gene (beta 39CAG----TAG) in delta beta zero-thalassemia. These data strengthen the suggestion that -196 mutation is causally linked to the abnormal phenotype and raise the question of whether the same or multiple mutational events are responsible for the appearance of the -196 mutation in different syndromes.

Base Sequence↗
PubMed1986

Italian type of deletional hereditary persistence of fetal hemoglobin.

We report a new type of deletion of the beta globin gene cluster in the Italian population that confers a phenotype of hereditary persistence of fetal hemoglobin (HPFH) to the carriers. This deletion begins approximately 5 kilobases (kb) 5' to the delta globin gene and ends approximately 30 kb 3' to the beta globin gene, in close proximity to the 3' end of an Indian HPFH. In all four previously described HPFH, a repetitive Alu I region 5' to the delta globin gene is largely or completely deleted; the 5' end of the new HPFH is consistent with this common feature. In addition, the finding that Italian and Indian HPFHs, as reported for other groups of deletions, have very close 3' ends, strengthens the idea that common mechanisms may operate in generating these deletions. Finally, we show that, in spite of similar 5' breakpoints, the deletion of Spanish delta beta(0)-thalassemia is at least 8 kb longer than that of Negro HPFH type I, thus ruling out the hypothesis that the overall extent of the deletion might influence the level of gamma globin chain synthesis.

Chromosome Deletion↗