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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human T-cell leukemia virus type 1 (HTLV-I) is associated with adult CD4+ T-cell leukemia (ATL) and tropical spastic paraparesis (TSP). In as much as only a small percentage of individuals infected with HTLV-I develop either disease, we set out to model a genetic partner for this virus in an effort to understand and possibly reproduce its pathophysiology. To this end we have developed a binary set of transgenic mice, one bearing the relatively inactive HTLV-I long terminal repeat (LTR) positioned to drive the c-myc oncogene and another bearing a fusion transgene consisting of the immunoglobulin promoter/enhancer driving the gene for the HTLV-I transcription activator, tax. Alone, the tax construct, though expressed in the thymus, spleen, lung and brain, has no deleterious effect. Alone, the HTLV-I LTR/c-myc construct is expressed at very low levels in lymphoid cells and occasionally induces lymphomas in older animals. When these two transgenic lines are mated, bigenic offspring harboring both transgenes exhibit dramatic tumor formation. As in the human, these animals develop CD4+ T-cell lymphomas, but they also develop central nervous system tumors by 25-90 days of age. The syndrome, which is 100% penetrant and lethal, provides an animal model for adult T-cell lymphoma and a source of cultured cells of neurogenic origin.
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PMID:Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes. 146 48

Transforming growth factor-Beta (TGF-beta) is a potent growth inhibitor for several cell types including epithelial cells and hematopoietic progenitor cells. Using a human promonocytic leukemia cell line, THP-1, we have shown that TGF-beta inhibits their proliferation and promotes differentiation into cells exhibiting macrophage-like properties. Therefore, a key question is whether TGF-beta influences the expression of genes associated with proliferation and/or growth inhibition. TGF-beta treatment of THP-1 cells results in downregulation of expression of c-myc. We also observe that TGF-beta 1-treated cells express reduced levels of the cell cycle regulated histone, H2B, but express elevated levels of an RNA splicing variant of this histone that has been observed to be upregulated in growth inhibited and terminally differentiated cells. In addition, a nuclear protein associated with senescence and withdrawal of cells from the cell cycle, statin, is also expressed by THP-1 cells in response to TGF-beta 1 treatment. These results suggest that TGF-beta 1 is capable of inducing expression of specific nuclear proteins associated with differentiation and/or cessation of proliferation that may result in changes in nuclear organization and altered gene expression. Such changes in nuclear organization may be incompatible with continued proliferation of the cells.
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PMID:Transforming growth factor-beta 1 induces expression of statin during differentiation of human promonocytic leukemia cells. 146 65

MuLV-integration sites were analyzed on seventeen thymic leukemia cell lines which have been established from spontaneous thymic leukemias in AKR mice and bone marrow chimeras. Three proviral integration sites were identified; near c-myc, N-myc and pim-1. Among them the integrations near the N-myc were analyzed. Two cell lines from AKR and a cell line from [(BALB/c x B6) F1-->AKR] bone marrow chimera contained the proviral integration near N-myc. In all three cell lines the integration of the provirus was found 18 to 20 bp downstream of the translational termination codon. The partial sequence analysis of the integrated LTR cell line established from AKR thymic lymphomas was the same as AKV. In contrast, the LTR integrated in a cell line from a bone marrow chimera was different from that of MuLV so far reported.
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PMID:[Activation of N-myc gene in leukemia cell lines derived from spontaneous murine lymphomas]. 148 82

The effects of deregulated expression of the human c-myc and MC29 v-myc oncogenes have been examined in a murine myelomonocytic cell line J774 (c-myc) and in a variety of myelomonocytic cell lines of different degrees of maturity generated from primary hematopoietic tissue (v-myc). Introduction of a Moloney murine leukemia virus long terminal repeat (LTR) c-myc construct into J774 cells resulted in constitutive expression of the exogenous myc gene and a concomitant increase in the degree of transformation and tumorigenicity of the cells. In addition, constitutive expression of exogenous myc inhibited induced differentiation of these cells by a variety of treatments including addition to the medium of lipopolysaccharide (LPS) or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) as well as complete withdrawal of serum from the medium. The degree of increased transformation, tumorigenicity and inhibition of terminal differentiation was dependent upon the level of exogenous myc expression. For the v-myc-generated myelomonocytic cell lines, introduction of v-myc resulted in a high degree of transformation and, irrespective of the differentiation status of the cells, a block of induced differentiation. These results indicate that the level of constitutive myc expression can affect the transformed phenotype, tumorigenicity and differentiation inducibility of myelomonocytic cells.
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PMID:Constitutive expression of exogenous myc in myelomonocytic cells: acquisition of a more transformed phenotype and inhibition of differentiation induction. 150 91

A highly malignant human T-cell leukemia was identified by cell surface analysis as a member of the T-cell receptor (TCR) gamma delta lineage. Cytogenetic and molecular analysis showed a novel t(8;14)(q24;q11) rearrangement involving the J delta 1 gene segment on chromosome 14 and the distal end of chromosome 8 near the c-myc proto-oncogene locus. The gamma delta TCR of the leukemia blasts was functionally intact and could be activated to generate intracellular calcium flux and to target Fc receptor-mediated redirected tumor cell lysis. In addition, non-major histocompatibility complex restricted lysis of a limited target cell panel was shown by fresh leukemic blasts and by the in vitro-maintained leukemia cells that was comparable to known T-cell lines with natural killer-like activity. These data suggest that the T-cell leukemia potentially had in vivo functional cytolytic activity. However, whether this activity did contribute to the patient's clinical condition could not be determined.
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PMID:A gamma delta+ T-cell leukemia bearing a novel t(8;14)(q24;q11) translocation demonstrates spontaneous in vitro natural killer-like activity. 153 37

The treatment of human myeloid leukemia cell lines with phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), is associated with loss of proliferative capacity and induction of monocytic differentiation. The present results demonstrate that treatment of asynchronous human U-937 leukemia cells with 10 nM TPA is also associated with oligonucleosomal DNA cleavage. This pattern of DNA fragmentation, which is observed in programmed cell death, was detectable in populations of TPA-treated cells that had entered a nonproliferative G0/G1 phase. Similar findings were obtained after TPA treatment of a synchronous population of G1 cells. These cells progressed through S and G2/M phases before undergoing internucleosomal DNA cleavage during G0/G1 arrest. These G0/G1 cells displayed characteristics of monocytic differentiation, including down-regulation of c-myc expression and induction of c-fms transcripts. DNA fragmentation was also studied in cells treated with 5 nM TPA for 48 h and then monitored in drug-free long-term culture. Endonucleolytic cleavage was similarly observed in the differentiated G0/G1 population. However, longer periods of culture were associated with a decrease in DNA fragmentation to undetectable levels. This effect was followed by retrodifferentiation and reentry of cells into cycle. Taken together, these findings demonstrate that internucleosomal DNA fragmentation occurs during induction of monocytic differentiation, and that both of these events are detectable in G0/G1 cells.
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PMID:Internucleosomal DNA fragmentation during phorbol ester-induced monocytic differentiation and G0/G1 arrest. 154 83

Bone marrow (BM) cells from two transgenic mice carrying the human c-myc oncogene were separately harvested, and each sample was injected into 25 lethally irradiated mice. We observed the contribution of the myc gene to the occurrence of hemopoietic neoplasms in the BM-repopulated mice, establishing a new experimental system for analyzing oncogene expression in the hemopoietic system in vivo. The hybrid gene that was transferred into the original transgenic mice was a combination of the human c-myc gene with a regulatory unit consisting of a murine immunoglobulin-heavy chain with an SV40 early-T promoter gene (Ig/Tp-myc). Among the transgenic lines, the tested BM cells were chosen from two lines that had been low-prone in leukemia; in these lines hemopoietic neoplasms did not appear for greater than or equal 200 days after birth. Lethally irradiated controls received BM cells from litters of transgenic mice that did not carry c-myc. The lifetime incidence of hemopoietic neoplasms was 94% and 91% in the two groups of mice repopulated with myc+ BM. By contrast, only 15% of control mice with myc- BM developed hemopoietic lesions. The incidence of hemopoietic malignancies combined with nonthymic lymphomas and myeloma cases (88% and 65%) was higher in the repopulated mice than the incidence of pre-B cell lymphomas in the original transgenic lines (56%). Thirty-two of the 40 myc+ mice that were examined showed the presence of the transferred gene in either the normal hemopoietic tissue or in the hemopoietic neoplasm. Furthermore, 18 of 22 hemopoietic neoplasms studied by Northern hybridization expressed mRNA from the transgenic gene; in other four neoplasms, expression was weak or absent.
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PMID:Hemopoietic neoplasms in lethally irradiated mice repopulated with bone marrow cells carrying the human c-myc oncogene: a repopulation assay. 154 84

We have utilized fibroblast cell lines to investigate myc-mediated cell transformation and tumour progression. Deregulated myc alleles were introduced into the rat fibroblast cell line, Rat-1, and a partially-transformed derivative of this cell line termed Rat-1 (PT). A human c-myc gene coupled to the Moloney murine leukemia virus long terminal repeat was introduced into both cell lines by transfection. The avian MC29 v-myc gene was introduced into the Rat-1 cell line by retroviral infection using a Moloney murine leukemia recombinant retrovirus. For both cell lines, the introduction of exogenous myc genes resulted in an increased degree of transformation. For the non-tumorigenic Rat-1 cell line, this also resulted in the acquisition of tumorigenicity, while for the Rat-1 (PT) cell line the degree of tumorigenicity was increased. Various clones were isolated and, for both human c-myc and avian v-myc, the level of myc expression correlated with the degree of transformation and the tumorigenic potential of the cell lines. In addition, both these parameters could be increased by passaging through syngeneic recipients. Our data show that tumour progression may be driven by the deregulated expression of myc genes; that transformation and tumorigenicity correlate with the level of exogenous myc expression; that additional events involving both in vitro and in vivo selection are involved in this process; and that myc expression may increase the cells' metastatic capacity.
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PMID:An in vitro fibroblast model system to study myc-driven tumour progression. 156 36

ABL-MYC, a murine retrovirus that encodes the v-abl and c-myc oncogenes, was constructed from Abelson murine leukemia virus (A-MuLV) in order to assess the biological consequences of co-expression of these genes in lymphoid cells. When inoculated into mice this retrovirus induced plasmacytomas in up to 100% of infected mice and less frequently induced pre-B lymphomas. Both tumor types contained genome-length proviruses in one or a few chromosomal locations, were mono- or oligoclonal as judged by immunoglobulin gene rearrangement and had unrearranged endogenous c-myc loci. The type of tumor induced depended upon the age and strain of mouse, and whether helper virus was present in the inoculated virus pool. ABL-MYC induced plasmacytomas with or without helper virus, with or without pretreatment of the mice with pristane, and in strains of mice resistant to pristane-induced plasmacytomas. Pristane treatment prior to ABL-MYC infection shortened the latent period of plasmacytomagenesis and produced mostly IgM-secreting tumors rather than IgA-secreting tumors, which predominantly arose in the absence of pristane. Control viruses for ABL-MYC with either a deletion in v-abl or a frameshift mutation in c-myc caused predominantly monocyte/macrophage tumors and pre-B-cell lymphomas respectively. Histopathological analysis of ABL-MYC-infected mice showed foci of transformed plasma cells as early as 14 days after infection. These results indicate that v-abl and c-myc act synergistically to transform mature B cells with high efficiency.
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PMID:A retrovirus that expresses v-abl and c-myc oncogenes rapidly induces plasmacytomas. 156 79

Transgenic mice bearing a mutant, activated N-ras oncogene directed to express within hematopoietic cells by an immunoglobulin enhancer (E mu) sporadically develop T-cell lymphomas and non-lymphoid tumors that may be of macrophage origin. To identify genes that can collaborate with N-ras in hematopoietic neoplasia, Moloney murine leukemia virus was used as an insertional mutagen. Infection of newborn E mu-N-ras mice with the virus greatly accelerated tumorigenesis, and nearly all the tumors proved to be T-cell lymphomas. Their variable surface phenotype (CD4+CD8-, CD4+CD8+ and CD4-CD8-) suggested that cells at several stages of T-cell development were susceptible to tumorigenesis. Southern blot analysis revealed that 68% of the tumors bore a proviral insert 5' to the c-myc gene, while 13% had an insert within the 3' untranslated region of the N-myc gene. Insertion was associated with elevated expression of these genes. Hence, activation of a myc gene appears to be the dominant pathway to tumorigenesis by insertional mutagenesis in lymphoid cells expressing a mutant ras gene. However, since many of the tumors were not transplantable, even the partnership of myc and ras may not suffice for full lymphoid malignancy.
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PMID:Retroviral infection accelerates T lymphomagenesis in E mu-N-ras transgenic mice by activating c-myc or N-myc. 157 Jan 58


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