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Biomedical subjects

L Bottero

Publications and source records attributed to L Bottero.

32 records · Page 2Linked to original sources
PubMed1986

Expression of cellular oncogenes in primary cells from human acute leukemias.

The structure and the expression of 11 cellular oncogenes (protooncogenes) were analyzed in primary cells from 20 acute lymphocytic (ALL) and 31 acute myelogenous (AML) leukemia patients. Neoplastic cells, obtained prior to initiation of therapy, were purified and classified, on the basis of both surface antigen pattern and morphology, into pre-B, B, and T ALL and M1-M5 AML. RNA was extracted and analyzed for expression of cellular oncogenes coding for nuclear proteins (c-myc, c-myb, c-fos), the beta-chain of platelet-derived growth factor (c-sis), growth factor receptors or related proteins (c-src, c-abl, c-fes, c-erbB), or putative intermediate transducers of mitogenic signals (c-Ha-ras, c-Ki-ras, c-N-ras). Quantitative analysis of total RNA was carried out by dot blot hybridization to specific cDNA or genomic probes. Number and size of transcripts were evaluated by blot hybridization of electrophoretically fractionated poly(A)+ RNA. Expression of c-myc and c-myb was detected in all leukemic cells at variable levels and was characterized by well-defined patterns within ALL subtypes. Conversely, significant levels of c-fos transcripts were detected only in myelomonocytic (M4) and monocytic (M5) leukemias. Among the "src-family," c-fes was expressed more in AML than ALL, and c-abl was expressed at variable but not elevated levels in all leukemia types. c-Ha-ras was uniformly expressed at low levels, as in non-neoplastic cells. c-Ki-ras transcription was detected only in T ALL; N-ras expression was barely demonstrable. The structure of these protooncogenes was not grossly modified, as evaluated by Southern analysis, except for c-myc rearrangement in B ALL. These studies indicate that cellular oncogene expression in specific subtypes of leukemic cells may relate to either the proliferative activity (c-myc, c-myb) or the differentiation state (c-fos) of the cells, or possibly to expression of receptors for putative hemopoiesis-related growth factors (c-fes, c-abl). Our data provide a basis for in-depth analysis of protooncogene expression in normal and neoplastic hemopoiesis.

DNA, Neoplasm↗
PubMed1984

Translocation and rearrangement of c-myc into immunoglobulin alpha heavy chain locus in primary cells from acute lymphocytic leukemia.

We report the molecular analysis of an 8;14 reciprocal chromosome translocation in a case of acute lymphocytic leukemia (L3 type). DNA from primary leukemic cells was analyzed on the basis of restriction endonuclease mapping by hybridization with various human c-myc and Ig heavy chain probes. The breakpoint of the translocation is within an approximately equal to 200-base-pair region in the first intron of the c-myc gene. The first, untranslated exon thereby remains on chromosome 8q-, whereas the whole protein-coding region is rearranged in the C alpha 1 locus on chromosome 14q+. RNA transfer blot analysis showed high levels of at least two different c-myc transcripts originated from the translocated gene. Both differ in size from the normal 2.2- and 2.4-kilobase transcripts. Both c-myc structure and expression were apparently normalized in remission phase. These studies demonstrate rearrangement and abnormal expression of c-myc in primary cells from an acute leukemia patient, thus adding to the concept of a key role for c-onc in human oncogenesis.

Adolescent↗
PubMed1984

Subpopulation heterogeneity in human acute myeloid leukemia determined by monoclonal antibodies.

The leukemic population in 63 patients with acute myeloid leukemia (AML) was studied with 15 monoclonal antibodies that detect lineage-related and stage-related antigens on normal hemopoietic cells. Indirect immunofluorescence and fluorescence-activated cell sorting showed that subpopulations of leukemic cells reacted with some or all antibodies, but the percentage of cells reacting with a single antibody varied widely among patients. The composite antigenic phenotype of the various cases, as determined by immunofluorescence assay, did not correlate with the French-American-British morphological classification. Furthermore, some cells in each case failed to express any antigen normally expressed on myelomonocytic precursors from the level of the early CFU-GM to the mature granulocyte or monocyte. In double-fluorescence experiments, the individual cells expressed none, one, or both antigens. These results demonstrate that there is considerable subpopulation heterogeneity in AML. This heterogeneity may considerably limit or complicate the use of monoclonal antibodies for diagnosis, prognosis, and treatment of acute nonlymphocytic leukemia (ANLL).

Adult↗
PubMed1983

Differentiation antigens of human hemopoietic cells: patterns of reactivity of two monoclonal antibodies.

Two mouse anti-human monoclonal antibodies (S3.13 and S5.7) raised against cells of acute myelogenous leukemia were found to react with antigens expressed on the surface of subsets of monocytes and lymphocytes. S3.13 precipitates a peptide of Mr 29,000, and S5.7 precipitates a peptide of Mr 20,000 present on the surface of all the cell types tested. These two surface antigens were distributed on discrete subpopulations of normal hemopoietic cells. The antibodies reacted with all (S5.7) or a subpopulation (S3.13) of peripheral blood T-lymphocytes, and with a subset of monocytes. Both antibodies reacted with bone marrow blast cell progenitors of the myelomonocytes and erythroid lineage. S5.7 also reacted with non-T-lymphocytes and with cells of the eosinophilic lineage. Both antigens disappeared from the cell surface during normal myeloid and erythroid differentiation. Thus, these monoclonal antibodies define the molecular characteristics and the cellular distribution of two differentiation antigens present on cells of the hemopoietic lineage.

Animals↗
PubMed1983

Human granulocyte surface molecules identified by murine monoclonal antibodies.

We have investigated the nature of the antigens recognized by four classes of mouse anti-human monoclonal antibodies that characteristically reacted with neutrophilic granulocytes and their precursor cells, but not with monocytes or other normal hemopoietic cells. The antigenic targets of the majority (9/12) of the independently isolated monoclonal antibodies were present on two surface glycoproteins (Mr 145,000 and 105,000) and glycolipids. This antigen(s) was also detected on granulocyte precursor cells, including the bone marrow granulocyte/monocyte progenitor cells (CFU-GM). The same antigen(s) detected by these monoclonal antibodies was also present in non-hemopoietic cell lines (colon carcinoma and neuroblastoma). Three other antigens, defined by monoclonal antibodies AHN-8, L12.2, and L13.1 and present on granulocytes and their mid-late precursor cells, could not be identified as proteins but were detected in a protein-free glycolipid extract of these cells. The diversity of the antigens was confirmed by cross-competition experiments and by the identification of their different patterns of reactivity with cell lines and bone marrow cells.

Animals↗
PubMed1982

Induction of differentiation of human myeloid leukemias by phorbol diesters: phenotypic changes and mode of action.

Treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) of acute myeloblastic leukemia cells halts proliferation and induces expression of monocyte/macrophage markers. Surface characteristics of leukemic HL60 cells, as defined using a panel of monoclonal antibodies, were found to be similar to those of normal human promyelocytes. TPA treatment, however, induced a phenotype that, unlike normal monocytes, contained several myeloid-specific markers and lacked several monocyte-specific markers. TPA treatment of HL60 cells causes the rapid disappearance of the transferrin receptor from the cell surface. Because transferrin is essential for HL60 cell proliferation in culture, the disappearance of this receptor is followed by an irreversible accumulation of the cells in the G1 phase of the cell cycle. The TPA-induced arrest of cell proliferation suggests the potential of this agent in experimentally treating myeloblastic leukemias.

Animals↗
PubMed1982

A monoclonal antibody with specificity for leukemic cells transformed by defective avian leukemia viruses.

Mouse anti-chicken monoclonal antibodies were raised against an avian myeloblastosis virus (AMV)-transformed myeloblastic leukemic cell line. One monoclonal antibody, S1-37 (IgG2a), reacted with producer and nonproducer myeloblastic leukemia cell lines transformed by AMV and by E-26 virus, but it did not react with chicken fibroblasts infected with RAV-2, MAV-2, MAV-1, or RAV-7. S1-37 also did not react with normal chicken hemopoietic cells, except for yolk sack macrophages and a small population of embryonal and adult bone marrow cells that morphologically resembled macrophages. Cytotoxicity studies of GM-CFU, the normal stem cell population of the granulocytic macrophage lineage, indicated that these cells lack the surface antigen recognized by S1-37. Immunoprecipitation studies of 125I surface-labeled myeloblastic leukemic cells indicated that S1-37 binds a 42,000 Mr polypeptide. The possible role of this polypeptide in the process of transformation and differentiation of chicken myeloid cells is discussed.

Animals↗
PubMed1982

A monoclonal antibody that detects expression of transferrin receptor in human erythroid precursor cells.

A monoclonal antibody, L5.1, obtained by immunizing a Balb/c mouse with HL60 human promyelocytic leukemia cells, was found to react with both HL60 cells and with the K562(S) cell line. This monoclonal antibody binds and immunoprecipitates a glycoprotein (Mr 87,000) present on the cell surface membrane of K562(S) as a disulfide bonded dimer. In competition experiments L5.1 competes with both transferrin and OKT9 (a known antitransferrin receptor antibody) for binding to target K562(S) erythroleukemia cells. Binding of both L5.1 and transferrin to the surface of K562(S) cells is inhibited by treatment with 12--O-tetradecanoyl-phorbol-13-acetate, and the extent and time course of inhibition is similar in both cases. Cell sorting analysis of normal human marrow cells incubated with L5.1 indicates that L5.1 reacts strongly with all the morphologically recognizable erythroid lineage precursors, from the pronormoblast to the orthochromatic normoblast, and with reticulocytes. Erythrocytes, myeloid elements, monocytes, megakaryocytes and platelets, peripheral blood B and T lymphocytes do not bind significantly with this antibody and only a small fraction of promyelocytes was reactive. Antibody L5.1 did not react with leukemic cells of patients with acute lymphoblastic, myeloblastic and promyelocytic leukemias, but it did react with some established B (1 of 5) and T (2 of 3) cell lines, and a myeloid (1 of 3) cell line, and with PHA-stimulated peripheral blood lymphocytes. The nonhemopoietic cell lines tested did not bind with L5.1 with the exception of a colorectal adenocarcinoma and a melanoma cell line, which were both strongly positive. The relationship of antibody L5.1 to other monoclonal antibodies that bind the transferrin receptor is discussed.

Animals↗
PubMedDate not supplied

A human homoeo box gene specifically expressed in spinal cord during embryonic development.

Several genes involved in the determination of Drosophila body segments share a conserved DNA sequence of 183 nucleotides termed the homoeo box. Homologous homoeo box sequences have been detected in the genome of species ranging from insects and anellids to vertebrates, and a number of homoeo box-containing genomic DNA clones have been isolated from Xenopus, mouse and human. We have recently isolated human complementary DNA clones containing homoeo box sequences, representing transcripts from four different genes. We report here the nucleotide sequence of one of these clones (HHO.c10) and show that the corresponding gene is transcribed in human embryos and fetuses at 5-10 weeks post-conception. A major polyadenylated transcript of approximately 2.1 kilobases (kb), as well as RNA species of higher relative molecular mass (Mr), are specifically expressed at a constant level in spinal cord throughout this developmental period.

Base Sequence↗