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Biomedical subjects

U Torelli

Publications and source records attributed to U Torelli.

At least 55 records · Page 3Linked to original sources
PubMed1987

Philadelphia-positive chronic myeloid leukemia with a chromosome 22 breakpoint outside the breakpoint cluster region.

In chronic myelogenous leukemia (CML) the reciprocal translocation resulting in the Philadelphia chromosome (Ph1) leads to the formation of a chimeric transcriptional unit carrying both c-abl and bcr genetic information whose transcript is a new fused mRNA of 8.5-kilobases (kb) and whose translational product is a 210-kD phosphoprotein with tyrosine kinase activity implicated in the pathogenesis of CML. Twenty patients affected by Ph1-positive CML were studied by Southern blot analysis with bcr. Unexpectedly, in three Ph1-positive patients, the breakpoint of chromosome 22 was located neither inside the bcr region nor 5' to it. Northern blot analysis of the RNAs of two of these patients showed the absence of a detectable 8.5-kb chimeric mRNA. In the third patient a chimeric mRNA was detected by a c-abl cDNA probe but failed to hybridize with a bcr cDNA probe and showed very low hybridization levels with further 5' bcr cDNA probes. The possibility is raised that in CML a breakpoint outside bcr might either still allow the formation of a chimeric mRNA, possibly through alternative splicing mechanisms, or might prevent the transcription of the chimera. In the latter case different molecular events resulting in the formation of a Ph1 chromosome may underlie the same myeloid neoplastic phenotype.

Adult↗
PubMed1986

Differential patterns of expression of cell cycle-related genes in blast cells of acute myeloid leukemia.

The expression of two G1-specific clones, p2A9 and p4F1, of two cell cycle-related oncogenes, c-myc and c-myb and of one S phase-specific gene, the H3 histone gene, was explored in 11 cases of acute myeloid leukemia. Both Northern blot analysis and in-situ hybridization were employed. Differential patterns of gene expression were observed. In 6 out of 11 cases a considerable or high expression of the p2A9 and p4F1 clones and of c-myc and c-myb oncogenes was observed. In 2 cases a high expression of c-myc was matched by low or absent expression of the other genes examined. In 3 cases the expression of 2A9, 4F1, c-myc and c-myb was very low or undetectable. In two of these cases a considerable expression of the H3 histone gene was observed.

Histones↗
PubMed1986

Cellular levels of mRNA from c-myc, c-myb and c-fes onc-genes in normal myeloid and erythroid precursors of human bone marrow: an in situ hybridization study.

The expression of three onc-genes, c-myc, c-myb and c-fes, has been evaluated at the cellular level in myeloid and erythroid precursors of normal human bone marrow, by "in situ" hybridization with tritium-labelled probes. A relatively large amount of m-RNA from the three onc-genes was detected in myeloblasts and promyelocytes, but whereas the expression of c-myc and c-myb decreased in more advanced stage of maturation of the myeloid lineage, c-fes mRNA remained at a relatively high level until the granulocyte stage. c-myc and c-myb were expressed at a fairly high level in basophilic erythroblasts, which also showed low levels of c-fes mRNA. No expression of these onc-genes was detectable in more mature erythroblasts. Megakaryocytes showed high levels of m-RNA from all three onc-genes. Our results suggest that c-myc and c-myb expression is related in some way to the cellular proliferation of myeloid and erythroid precursors, whereas c-fes expression is more restricted to myeloid differentiation.

Bone Marrow Cells↗
PubMed1986

Platelet alpha-granule release in chronic myeloproliferative disorders with thrombocytosis.

Platelet alpha-granule release in 22 patients affected by chronic myeloproliferative disorders with thrombocytosis and seven subjects with thrombocytosis secondary to splenectomy were studied. We found elevated beta-thromboglobulin (BTG) and platelet factor 4 (PF4) plasma levels in all patients. Intraplatelet content of BTG and PF4 was decreased in patients with idiopathic thrombocythaemia (IT) and idiopathic myelofibrosis (IMF). The BTG and PF4 results were also expressed as the ratio plasma BTG and PF4: whole blood platelet count. In patients with IT, BTG: whole blood platelet count ratio was low, conversely, the same ratio was high in patients with IMF. In conclusion, our results suggest the presence of an abnormal, BTG-deficient clone in IT and a peripheral platelet activation in IMF.

Beta-Globulins↗
PubMed1985

Study of the levels of expression of two oncogenes, c-myc and c-myb, in acute and chronic leukemias of both lymphoid and myeloid lineage.

Total cellular RNA from a series of leukemic cell populations, both myeloid and lymphoid, as well as from normal circulating lymphocytes was analysed for the expression of two cellular oncogenes, c-myc and c-myb, by Northern blot hybridization assay. Expression of c-myc but not of c-myb was observed in unstimulated normal lymphocytes. Stimulation by PHA was shown to activate the expression of both genes. Remarkably different levels of expression of c-myc were observed in ALL, whereas in CLL the expression of c-myc was uniformly low or absent. Differential expression of c-myc was detected in AML as well as in CML, c-myb was differentially expressed in AML and ALL, and absent in CLL and CML. Other single cases of hemopoietic disorders were studied, but the expression of the two oncogenes was low or absent. Neither evident genome amplification nor genome rearrangements were detected in the cell DNAs digested with restriction endonucleases.

DNA, Neoplasm↗
PubMed1985

Expression of human c-fes onc-gene occurs at detectable levels in myeloid but not in lymphoid cell populations.

Total cellular RNA from a variety of myeloid and lymphoid cell populations, normal and leukaemic, was analysed for the expression of a human cellular onc-gene, c-fes, by northern blot hybridization assays. The probe used was a molecularly cloned human DNA sequence homologous to the 5' terminal sequence of v-fes. All the myeloid cellular populations expressed the c-fes gene. In some cell populations at an advanced stage of differentiation (circulating leucocytes from Chronic myeloid leukaemia (CML), HL60 cells induced to differentiate by retinoic acid) the level of expression was even higher than in early stages of the myeloid lineage (blast cells from AML, uninduced HL60 cells). No transcript of the c-fes gene was detected in the different lymphoid populations studied. The occurrence of an RNA complementary to the c-fes sequence appears sufficiently characteristic of a myeloid population to distinguish it from a lymphoid population, normal and leukaemic.

Cell Differentiation↗
PubMed1985

Activation of c-myb expression by phytohemagglutinin stimulation in normal human T lymphocytes.

The expression of c-myb in normal human T lymphocytes directly derived from a normal subject and not adapted to continuous growth in culture was found to be markedly increased after phytohemagglutinin stimulation. In the same cells, the expression of c-myc mRNA is a much earlier event compared with the appearance of c-myb mRNA, which takes place soon after that of histone H3 mRNA. The increase in c-myb expression was not due to a particular T-lymphocyte subset, as shown by in situ hybridization assays.

Cells, Cultured↗
PubMed1984

Sequence complexity and diversity of polyadenylated RNA molecules transcribed in human myeloid cells. Leukemic myeloblasts and HL60 promyelocytes uninduced and induced to terminal differentiation with retinoic acid.

The kinetic composition of the polyadenylated RNAs of leukemic myeloblasts and HL60 promyelocytes was examined by the cDNA-poly (A) +RNA reassociation technique before and after the induction of differentiation with retinoic acid. The data obtained in the homologous hybridizations show the following main features: the sequence complexity of the total poly(A) +RNA molecules is 72,000 different sequences in leukemic myeloblasts, 64,000 in HL60 promyelocytes before induction and 26,000 after treatment of HL60 with retinoic acid; the number of sequences reacting as abundant is clearly higher in HL60 promyelocytes (5,000) than in leukemic myeloblasts (1,000), and the number decreases sharply after induction (300); the repetition frequency of the abundant and rare components is almost unchanged between leukemic myeloblasts and HL60 promyelocytes, while it is markedly increased after induction with retinoic acid. The heterologous reactions show that the observed differences in complexity are mainly related to the missing of rare sequences. Moreover, an important portion of sequences already present in leukemic myeloblasts has a definitely higher repetition frequency in HL60 promyelocytes. Finally, the most abundant sequences in HL60 cells after induction are already present before treatment. The data presented here suggest that, during human myeloid differentiation, important, possibly transcriptional, regulatory mechanisms of gene expression are active long after the first commitment event of the hemopoietic undifferentiated stem cell.

Adult↗
PubMed1981

Sequence complexity and diversity of polyadenylated RNA molecules of human normal resting, PHA-stimulated and leukemic lymphocytes.

The abundance and complexity of total poly(A)+RNA of human normal unstimulated lymphocytes, PHA-stimulated and leukemic lymphocytes were examined using the cDNA-poly(A)+ RNA hybridization technique. It was found that in both PHA-stimulated and leukemic lymphocytes the complexity of total poly(A)+RNA is strongly reduced in respect to normal unstimulated lymphocytes. The differences is due to a small portion, by weight, of high complexity sequences, suggesting the involvement or nuclear, not necessarily transcriptional, events. Moreover the heterologous hybridizations show that: 1) in PHA-stimulated lymphocytes there is a set of highly abundant sequences which are represented in normal and leukemic lymphocytes at a very reduced rate; 2) the sequences abundant in normal unstimulated lymphocytes are less represented in leukemic lymphocytes; the converse also is true, but at a lower extent. On the basis of available data, it is suggested that the observed changes in the abundance pattern of PHA-stimulated lymphocytes may be related mainly to a difference in the half-life of the mRNAs, while those of leukemic lymphocytes require some transcriptional or post-transcriptional nuclear event.

Base Sequence↗
PubMed1979

Kinetics of hybridization to human DNA of heterogeneous nuclear RNA isolated from normal human lymphoblasts and acute leukemia blast cells.

Heterogeneous nuclear RNA was extracted from normal PHA-stimulated human lymphocytes and acute myeloid leukemia blast cells. Experiments were performed to determine the hybridization kinetics of these RNA's to human DNA. The best least squares solutions indicate in the hybridization reaction of both normal and leukemic RNA two main components. For leukemic cell RNA the rate constants of both components were significantly different from that of normal cell RNA. In particular, the difference between the rate constants of the second lower component suggests that the slowly hybridizing sequences in leukemic cell RNA have a degree of repetition higher than of the corresponding sequences of normal cell RNA.

Base Sequence↗
PubMed1979

Reassociation kinetics of the DNA of human acute leukemia cells.

Human DNA isolated from normal phytohaemagglutinin-stimulated human lymphocytes and from acute leukemia blast cells have been studied by renaturation techniques using hydroxyapatite binding and DNA hyperchromism. In the leukemic genome, the unique sequences account for 62% of the genome of leukemic DNA. Repetitive sequences may be subdivided into at least three fractions: (a) foldback sequences, which represent 5% of the genome; (b) sequences with high repetition frequency (3. 10(4) times on the average), which represent 12% of the genome; (c) sequences with low repetition frequency (10 times on the average), which represent 16% of the genome. The average length of the repetitive sequences is evaluated to be between 200 and 500 nucleotides. There are at least two patterns of interspersion of repetitive sequences with unique sequences of different length: short (about 2000 nucleotides on average) and long (not defined). The results of our experiments on DNA from normal phytohaemagglutinin-stimulated human lymphocytes are in close agreement with those reported by other authors studying different types of human cells. The human leukemic DNA, as far as the parameters that have been studied, does not significantly differ from normal human DNA.

Acute Disease↗
PubMed1979

Recovery from aplastic anemia after treatment with antilymphocyte globulin.

A 16-year-old boy with aplastic anemia that was resistant to treatment with androgens and prednisone and that had a high transfusion requirement was treated with antilymphocyte globulin. A complete normalization of the hematologic values was obtained. The result supports the theory of immune pathogenesis in some cases of aplastic anemia.

Adolescent↗